Tunable nanofiber filter media and filter devices

ABSTRACT

A tunable nanofiber filter device can include a filter housing defining an interior space, the housing having defined therein and inlet and an outlet, each in fluid communication with the interior space, and a plurality of filter laminas disposed within the interior space, each filter lamina including an upper surface, a lower surface, and an aperture defined therethrough. The plurality of filter laminas can be arranged in a stack wherein the opposing surfaces of adjacent filter laminas define a portion of an interlaminar flow space extending between the opposing surfaces. The flow space can be in fluid communication with the apertures of corresponding adjacent filter laminas to form a continuous flow passage extending through the lamina stack from the inlet to the outlet. An array nanofibers can extend into the flow passage from a portion of each filter lamina such that a fluid flowed through the flow passage flows across a portion of said array.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationSer. No. 62/217,550, entitled ULTRA SMALL FIBERS AS FILTER MATERIALS,filed Sep. 11, 2015, the entire disclosure of which is herebyincorporated herein by this reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

REFERENCE TO SEQUENCE LISTING OR COMPUTER PROGRAM LISTING APPENDIX

Not Applicable.

TECHNICAL FIELD

The present disclosure relates generally to filter media and filterdevices, and more specifically to filter media and filter devices whichcombine user-defined arrays of nanofibers and layers of modular laminasto form flow passages having tuned nanoscale topographies specific toone or more preselected retentates.

BACKGROUND OF THE INVENTION

Fibrous filter media are used in various types of filter devices to traplarge and small particles in liquid and gas streams. Such filter mediaare typically formed from multiple layers of coarse and fine fibersextending parallel to an upstream face surface of the filter media. Anouter layer of coarse fibers forms a bulk filtration layer for filteringof larger particles, while an inner or underlying layer of fine fibersprovides filtering of small particles. Fine fibers are often provided ina thin layer laid down on a supporting substrate or used with one ormore protective layers to obtain a variety of benefits, includingincreased efficiency, reduced initial pressure drop, cleanability,reduced filter media thickness, and to provide an impermeable barrier tovarious liquids, such as water. However, prior approaches have severalinherent disadvantages, including the need for a supporting substrate, arisk of delamination of the fine fiber layer from the substrate, morerapid loading of the filter by captured particles, and the alignment offine fibers parallel to the media face surface.

On the molecular level, fibrous materials also trap contaminants withelectrostatic forces, including ionic bonding, hydrogen bonding, and Vander Waals forces. These electrostatic interactions occur on the fibersurface. Because these interactions are known to increase non-linearlyat sub-micron length scales, functional improvement in fibrous filtermedia is largely based on minimizing denier (linear mass density orfiber diameter). Although the production of filter media comprising veryfine fibers having a high surface-to-volume ratio, such as microfibersand nanofibers, has recently been emphasized in the industry, processinglimitations associated with traditional methods of producing such fiberslimit the utility of these materials in filtration applications. Forexample, extruded microfibers require the use of solvents and, oralternatively, immiscible polymer blends to split fibers to submicronlength scales, while production of nanofibers by the electrospinningmethod requires high-voltage (i.e., kilovolt) electric fields.

Accordingly, what is needed are improvements in filter media and filterdevices.

BRIEF SUMMARY OF THE INVENTION

The presently disclosed subject matter overcomes some or all of theabove-identified deficiencies of the prior art, as will become evidentto those of ordinary skill in the art after a study of the informationprovided in this document.

Disclosed herein are filter media and devices for filtering orseparating a contaminant from a fluid liquid or gas stream whichincorporate flow passages formed by layered laminas comprising tunabletopographies of user-defined arrays of nanofibers and, optionally,nanoholes. Also disclosed herein are tunable nanofiber diffusion filtersfor dialysis which have multiple flow paths for a first and second fluidsuch as blood and dialysate, in which the flow paths are separated byadjacent diffusion zones formed of one or more arrays of freestandingnanofibers through which the first fluid and the second fluid interface.

Accordingly, in one aspect, the disclosure provides a filter mediacomprising an assembly of filter laminas, each filter lamina includingan upper surface, a lower surface, an array of nanofibers formed on aportion thereof, and an aperture extending from the upper surface to thelower surface, the filter laminas arranged in a stacked orientation suchthat the apertures define a portion of a flow passage extending throughthe assembly, the nanofibers extending into a portion of the flowpassage to form a tuned nanoscale topography specific to a preselectedretentate such that said retentate is filtered from a fluid containingthe retentate when the fluid is flowed through the flow passage.

In another aspect, the disclosure provides a filter device, comprising ahousing defining an interior space, the housing having defined thereinan inlet and an outlet, the inlet and outlet each in fluid communicationwith the interior space; a plurality of filter laminas disposed withinthe interior space, each filter lamina including an upper surface, alower surface, a first peripheral portion, a second peripheral portionopposite the first peripheral portion, a central region between thefirst and second peripheral portions, and an aperture defined throughthe first peripheral portion, the plurality of filter laminas arrangedin a stack wherein: the aperture of the uppermost lamina is in fluidcommunication with the inlet, the aperture of the lowermost lamina is influid communication with the outlet, and the opposing surfaces ofadjacent filter laminas define a portion of an interlaminar flow spaceextending between said opposing surfaces, the flow space in fluidcommunication with the apertures of the corresponding adjacent filterlaminas to form a continuous flow passage extending through the laminastack from the inlet to the outlet; and an array of nanofibers extendingfrom a portion of each filter lamina into the flow passage such that afluid flowed through the flow passage flows across a portion of saidarray.

In yet another aspect, the disclosure provides a diffusion filter fordialysis, comprising a housing defining an interior space, the housinghaving defined therein first and second inlets and first and secondoutlets, the inlets and outlets in fluid communication with the interiorspace; an assembly of laminas disposed within the interior space, thelamina assembly comprising a plurality of filter laminas, each filterlamina including a first and second slot defined therethrough, and aplurality of spacer laminas, each spacer lamina having a centralaperture defined therethrough, the filter and spacer laminas arrangedalternatingly in a stack wherein the central aperture of each spacerlamina defines an interlaminar space between opposing surfaces ofcorresponding adjacent filter laminas, the interlaminar space in fluidcommunication with the first and second slots of said adjacent filterlaminas such that the first slots form a first flow path extendingthrough the stack from the first inlet to the first outlet, and thesecond slots form a second flow path extending through the stack fromthe second inlet to the second outlet; a plurality of diffusion zonesformed in the interlaminar space, each diffusion zone comprising anarray of nanofibers extending into the interlaminar space from a portionof a corresponding adjacent filter lamina such that the array ofnanofibers separates the first and second flow paths throughout theinterlaminar flow space; wherein a first fluid flowed through the firstflow path interfaces across said diffusion zones with a second fluidflowed through the second flow path.

Numerous other objects, advantages and features of the presentdisclosure will be readily apparent to those of skill in the art upon areview of the following drawings and description of a preferredembodiment.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a plan view of a filter lamina for an embodiment of a tunablenanofiber filter formed in accordance with the present disclosure.

FIG. 2 is a partial sectional view of the filter lamina of FIG. 1 atline C-C.

FIG. 3 is an enlarged view of the filter lamina of FIG. 1 at inset A.

FIG. 4 is a perspective view of the filter lamina of FIG. 1.

FIG. 5 is an enlarged view of the filter lamina of FIG. 4 at inset B.

FIG. 6 is a perspective view of another filter lamina for an embodimentof a tunable nanofiber filter formed in accordance with the presentdisclosure.

FIG. 7 is a plan view of the filter lamina of FIG. 6.

FIG. 8 is an exploded perspective view of a stack of the filter laminasof FIGS. 1 and 6 for an embodiment of a tunable nanofiber filter.

FIG. 9 is a perspective view of the assembled lamina stack of FIG. 8.

FIG. 10 is a plan view of the lamina stack of FIG. 9.

FIG. 11A is a partial sectional view of the lamina stack of FIG. 10 atline A-A. Arrows indicate flow path.

FIG. 11B is a partial sectional view of the lamina stack of FIG. 10 atline B-B. Arrows indicate flow path.

FIG. 12A is a partial sectional view of the lamina stack of FIG. 10 atline C-C.

FIG. 12B is an enlarged view of the lamina stack of FIG. 12A at inset A.

FIG. 13 is a top perspective view of a first (lower) housing portion foran embodiment of a tunable nanofiber filter.

FIG. 14 is a bottom perspective view of the housing portion of FIG. 13.

FIG. 15 is a plan view of the housing portion of FIG. 13.

FIG. 16 is a side elevational view of the housing portion of FIG. 13.

FIG. 17 is a partial sectional view of the housing portion of FIG. 15 atline A-A.

FIG. 18 is a top perspective view of a second (upper) housing portionfor an embodiment of a tunable nanofiber filter.

FIG. 19 is a bottom perspective view of the housing portion of FIG. 18.

FIG. 20 is a side elevational view of the housing portion of FIG. 18.

FIG. 21 is a bottom plan view of the housing portion of FIG. 18.

FIG. 22 is a partial sectional view of the housing portion of FIG. 21 atline A-A.

FIG. 23 is a perspective view of an embodiment of a partially assembledfilter showing the first (lower) housing portion of FIG. 13 with thelamina stack of FIG. 9 positioned therein for assembly with the second(upper) housing portion of FIG. 18.

FIG. 24 is a plan view of the partially assembled filter of FIG. 23.

FIG. 25 is a partial sectional view of the partially assembled filter ofFIG. 24 at line A-A.

FIG. 26 is a partially exploded top perspective view of an embodiment ofa tunable nanofiber filter disclosed herein showing the partiallyassembled filter of FIG. 23 with the upper housing portion of FIG. 18positioned for assembly therewith.

FIG. 27 is a partially exploded bottom perspective view of the filter ofFIG. 26.

FIG. 28 is a perspective view of the assembled filter of FIG. 26.

FIG. 29 is a side elevational view of the filter of FIG. 28.

FIG. 30 is a plan view of the filter of FIG. 28.

FIG. 31 is a sectional view of the filter of FIG. 30 along line B-B.Arrows indicate flow path.

FIG. 32 is a perspective view of an array of nanofibers extending from aportion of a filter lamina for a tunable nanofiber filter disclosedherein.

FIG. 33 is a plan view of the nanofiber array of FIG. 32.

FIG. 34 is a side elevational view of the nanofiber array of FIG. 32.

FIG. 35 is a side elevational view of a portion of a flow passagedefined through a lamina stack of a tunable nanofiber filter disclosedherein.

FIG. 36 is a plan view of another filter lamina for an alternateembodiment of a tunable nanofiber filter.

FIG. 37 is a partial sectional view of the filter lamina of FIG. 36 atline A-A.

FIG. 38 is an enlarged view of the filter lamina of FIG. 36 at inset A.

FIG. 39 is a perspective view of the filter lamina of FIG. 36.

FIG. 40 is an enlarged view of the filter lamina of FIG. 39 at inset B.

FIG. 41 is a plan view of another spacer lamina for an alternateembodiment of a tunable nanofiber filter.

FIG. 42 is a partial sectional view of the spacer lamina of FIG. 41 atline A-A.

FIG. 43 is a perspective view of a top spacer lamina for an alternateembodiment of a tunable nanofiber filter.

FIG. 44 is an exploded perspective view of a lamina stack for analternate embodiment of a tunable nanofiber filter formed from aplurality of filter laminas of FIG. 36 and the spacer laminas of FIG.41.

FIG. 45 is a perspective view of the assembled lamina stack of FIG. 44.

FIG. 46 is a plan view of the lamina stack of FIG. 45.

FIG. 47 is a partial sectional view of the lamina stack of FIG. 46 atline A-A. Arrows indicate flow path.

FIG. 48 is a perspective view of an embodiment of a filter lamina havingdiscrete regions of tuned topography.

FIG. 49 is a perspective view of another embodiment of a filter laminahaving discrete regions of tuned topography.

FIG. 50 is a perspective view of yet another embodiment of a filterlamina having discrete regions of tuned topography.

FIG. 51 is a perspective view of a pair of opposing filter laminashaving discrete regions of tuned topography.

FIG. 52 is a perspective view of a second pair of opposing filterlaminas having discrete regions of tuned topography

FIG. 53 is an enlarged view of the opposing filter laminas of FIG. 52 atinset E.

FIG. 54 is an enlarged view of the opposing filter laminas of FIG. 52 atinset F.

FIG. 55 is an enlarged view of the opposing filter laminas of FIG. 52 atinset G.

FIG. 56 is an enlarged view of the opposing filter laminas of FIG. 52 atinset H.

FIG. 57 is an exploded perspective view of a subassembly of filterlaminas for an alternate embodiment of a tunable nanofiber filter havingdual flow paths. Solid arrows indicate primary flow path. Dashed arrowsindicate secondary flow path.

FIG. 58 is an exploded perspective view of a lower portion of a laminastack for an embodiment of a tunable nanofiber filter comprising two ofthe subassemblies of FIG. 57. Solid arrows indicate primary flow path.Dashed arrows indicate secondary flow path.

FIG. 59 is an exploded perspective view of an upper portion of a laminastack for an alternate embodiment of a tunable nanofiber filter. Solidarrows indicate the primary flow path.

FIG. 60 is an exploded perspective view of an alternate embodiment of atunable nanofiber filter having dual flow paths formed from the lowerlamina stack portion of FIG. 58 and the upper lamina stack portion ofFIG. 59.

FIG. 61 is a top perspective view of the tunable nanofiber filter ofFIG. 60 showing the assembled lamina stack positioned for assembly intoupper and lower halves of a filter housing.

FIG. 62 is a bottom perspective view of the tunable nanofiber filter ofFIG. 61.

FIG. 63 is a perspective view of the assembled tunable nanofiber filterof FIG. 60.

FIG. 64 is a side elevational view of the tunable nanofiber filter ofFIG. 63.

FIG. 65 is a perspective view of a filter lamina for an embodiment of atunable nanofiber diffusion filter formed in accordance with the presentdisclosure.

FIG. 66 is a plan view of the filter lamina of FIG. 65.

FIG. 67 is a perspective view of a spacer lamina for an embodiment of atunable nanofiber diffusion filter formed in accordance with the presentdisclosure.

FIG. 68 is a plan view of the spacer lamina of FIG. 67.

FIG. 69 is a perspective view of a lamina assembly for an embodiment ofa tunable nanofiber dialysis filter formed from a plurality of thefilter laminas of FIG. 65 and the spacer laminas of FIG. 67.

FIG. 70 is a plan view of the lamina assembly of FIG. 69.

FIG. 71 is a partial sectional view of the lamina assembly of FIG. 70 atline C-C.

FIG. 72 is a plan view of another filter lamina for an embodiment of atunable nanofiber diffusion filter.

FIG. 73 is a plan view of another lamina assembly for an embodiment of atunable nanofiber dialysis filter formed from a plurality of the filterlaminas of FIG. 72 and the spacer laminas of FIG. 67.

FIG. 74 is a partial sectional view of the lamina assembly of FIG. 73 atline A-A.

FIG. 75 is a plan view of yet another filter lamina for an embodiment ofa tunable nanofiber diffusion filter.

FIG. 76 is a plan view of yet another lamina assembly for an embodimentof a tunable nanofiber diffusion filter formed from a plurality of thefilter laminas of FIG. 75 and the spacer laminas of FIG. 67.

FIG. 77 is a partial sectional view of the lamina assembly of FIG. 76 atline A-A.

FIG. 78 is a partial exploded view of an embodiment of a tunablenanofiber dialysis filter showing the each of the lamina assemblies ofFIGS. 69, 73, and 76 positioned for assembly into upper and lower halvesof a filter housing.

FIG. 79 is a plan view of another filter lamina for another embodimentof a tunable nanofiber diffusion filter.

FIG. 80 is an exploded view of a lamina subassembly formed from aplurality of the filter laminas of FIG. 79 and the spacer laminas ofFIG. 67.

FIG. 81 is a perspective view of the assembled lamina subassembly ofFIG. 80.

FIG. 82 is a plan view of the lamina subassembly of FIG. 81.

FIG. 83 is another perspective view of the lamina subassembly of FIG.81. Dashed arrows indicate primary and secondary flow paths.

FIG. 84 is an exploded perspective view of a portion of tunablenanofiber diffusion filter showing a lamina stack showing a lamina stackcomprising the lamina subassembly of FIG. 80 ready for assembly into thebottom portion of a filter housing.

FIG. 85A is a plan view of a filter lamina for another alternateembodiment of a tunable nanofiber diffusion filter.

FIG. 85B is an enlarged view of the filter lamina of FIG. 85A at insetB.

FIG. 86 is a side elevational view of the filter lamina of FIG. 85A.

FIG. 87 is a plan view of an embodiment of a spacer lamina for use withthe filter lamina of FIG. 85A.

FIG. 88 is a perspective view of the spacer lamina of FIG. 87.

FIG. 89 is a plan view of the spacer lamina of FIG. 87 assembled on topof a filter lamina of FIG. 85A.

FIG. 90 is a side elevational view of the assembled laminas of FIG. 89.

FIG. 91 is an exploded view of a lamina subassembly formed from twofilter laminas of FIG. 85A and a spacer lamina of FIG. 87.

FIG. 92 is a perspective view of upper and lower portions of a housingfor an embodiment of a tunable nanofiber diffusion filter comprising thelamina subassembly of FIG. 91.

FIG. 93 is an exploded view of a tunable nanofiber diffusion filterformed from a plurality of the lamina subassemblies of FIG. 91 and thefilter housing of FIG. 92.

FIG. 94 is a plan view of the assembled filter of FIG. 93.

FIG. 95 is a side elevational view of the filter of FIG. 94.

FIG. 96 is a perspective view of the filter of FIG. 94.

FIG. 97 is a diagram depicting the filter of FIG. 94 in use.

FIG. 98 is a perspective view of another filter lamina for an alternateembodiment of the tunable nanofiber diffusion filter of FIG. 93.

FIG. 99 is a plan view of the filter lamina of FIG. 98.

FIG. 100 is an exploded view of a portion of a lamina stack for analternate embodiment of the tunable nanofiber diffusion filter of FIG.93. Spacer laminas are omitted.

FIG. 101 is a perspective view of another filter lamina for yet anotherembodiment of a tunable nanofiber diffusion filter.

FIG. 102 is a plan view of the filter lamina of FIG. 101.

FIG. 103 is a perspective view of a spacer lamina for use with thefilter lamina of FIG. 101.

FIG. 104 is a plan view of the spacer lamina of FIG. 103.

FIG. 105 is a perspective view of a lamina subassembly formed from aspacer lamina of FIG. 103 and a filter lamina of FIG. 101.

FIG. 106 is a plan view of the lamina subassembly of FIG. 105.

FIG. 107 is a plan view of another filter lamina for use in a laminastack with the filter lamina of FIG. 101.

FIG. 108 is an exploded view of a lamina stack for an alternateembodiment of a tunable nanofiber diffusion filter formed from twofilter laminas of FIG. 101, three spacer laminas of FIG. 103, and twofilter laminas of FIG. 107. Spacer laminas are omitted for clarity.

FIG. 109 is an exploded view of an embodiment of a tunable nanofiberdiffusion filter comprising the lamina stack of FIG. 108 and two halvesof a filter housing.

DETAILED DESCRIPTION OF THE INVENTION

The details of one or more embodiments of the presently disclosedsubject matter are set forth in this document. Modifications toembodiments described in this document, and other embodiments, will beevident to those of ordinary skill in the art after a study of theinformation provided herein. The information provided in this document,and particularly the specific details of the described exemplaryembodiments, is provided primarily for clearness of understanding and nounnecessary limitations are to be understood therefrom. In case ofconflict, the specification of this document, including definitions,will control.

The present disclosure relates to filter devices for removing acontaminant from a fluid stream. In a general embodiment, the tunablenanofiber filters disclosed herein are designed to filter a preselectedsubstance or contaminant from a fluid stream using one or moreuser-defined arrays of nanofibers, such as those described in U.S.2013/0216779 which is incorporated herein by reference in its entirety.

While the terms used herein are believed to be well understood by one ofordinary skill in the art, definitions are set forth herein tofacilitate explanation of the subject matter disclosed herein.

Unless define otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the subject matter disclosed herein belongs. Althoughany methods, devices, and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of the presentlydisclosed subject matter, representative methods, devices and materialsare now described.

The terms “a”, “an”, and “the” refer to “one or more” when used in thisapplication, including the claims. Thus, for example, reference to “acontaminant” includes a plurality of particles of the contaminant, andso forth. The use of the word “a” or “an” when used in conjunction withthe term “comprising” in the claims and/or the specification may mean“one,” but it is also consistent with the meaning of “one or more,” “atleast one,” and “one or more than one.”

All references to singular characteristics or limitations of the presentdisclosure shall include the corresponding plural characteristic(s) orlimitation(s) and vice versa, unless otherwise specified or clearlyimplied to the contrary by the context in which the reference is made.

All combinations of method or process steps as used herein can beperformed in any order, unless otherwise specified or clearly implied tothe contrary by the context in which the referenced combination is made.

The methods and devices of the present disclosure, including componentsthereof, can comprise, consist of, or consist essentially of theessential elements and limitations of the embodiments described herein,as well as any additional or optional components or limitationsdescribed herein or otherwise useful.

Unless otherwise indicated, all numbers expressing physical dimensions,quantities of ingredients, properties such as reaction conditions, andso forth used in the specification and claims are to be understood asbeing modified in all instances by the term “about”. Accordingly, unlessindicated to the contrary, the numerical parameters set forth in thisspecification and claims are approximations that can vary depending uponthe desired properties sought to be obtained by the presently disclosedsubject matter.

As used herein, the term “about,” when referring to a value or to anamount of mass, weight, time, volume, concentration, percentage or aphysical dimension such as length, width, or diameter, is meant toencompass variations of in some embodiments ±20%, in some embodiments±10%, in some embodiments ±5%, in some embodiments ±1%, in someembodiments ±0.5%, and in some embodiments ±0.1% from the specifiedvalue or amount, as such variations are appropriate to perform thedisclosed methods.

As used herein, ranges can be expressed as from “about” one particularvalue, and/or to “about” another particular value. It is also understoodthat there are a number of values disclosed herein, and that each valueis also herein disclosed as “about” that particular value in addition tothe value itself. For example, if the value “10” is disclosed, then“about 10” is also disclosed. It is also understood that each unitbetween two particular units are also disclosed. For example, if 10 and15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

As used herein, the term “fluid” is defined as any liquid or gas whichcan be passed through the filter media and filter devices disclosedherein. Multiple fluids having different specific gravities andviscosities can be used as well as gas and vapor streams, depending onthe application.

As used herein, the term “nanofiber” refers to a fiber structure havinga diameter of less than 1000 nanometers for more than half the length ofthe structure. In some embodiments, the nanofibers disclosed herein cancomprise a tapered base portion and a relatively longer fiber portionwhich extends from the base portion. In such embodiments, the fiberportion has a diameter of less than 1000 nm and a length greater thanthat of the base portion, and the base portion can have a diameter offrom about 10 μm to less than 1.0 μm. Additionally, in some embodiments,the base portion can also have a length of from about 1.0 μm to about 10μm, and the fiber portion can have a length of from about 10 to 100times greater than the length of the base portion. Nanofibers havinglarger diameter base portions in the range of from about 2.0 μm to about10 μm are best suited for applications wherein the bases must providestiffness to the nanofiber in the fluid stream.

In some preferred embodiments, nanofibers suitable for use in thetunable nanofiber filter media and filter devices disclosed herein canhave an overall length of from about 10 to about 100 μm. Accordingly,suitable nanofibers can also have a length to diameter ratio of from10:1 to about 1000:1. In one embodiment, the length to diameter ratio isfrom about 10:1 to about 100:1. By contrast, nanofibers known in theart, including electrospun nanofibers, melt-blown nanofibers andmicrofiber-derived nanofibers (i.e., microfibers split during processingto obtain sub-micron diameter structures), typically have much greaterlength to diameter ratios in the range of 1,000,000:1 to 100,000,000:1.As a result, the nanofibers used in tunable nanofiber filter media andfilter devices disclosed herein can have from about 10 to about 100times more tips per unit length than electrospun nanofibers, melt blownnanofibers and microfiber derived nanofibers.

The related terms “nanofiber array” and “array of nanofibers,” which areused interchangeably herein, collectively refer to a plurality offreestanding nanofibers of user-defined physical dimensions andcomposition integrally formed on and extending from a backing member,such as a film, according to user-defined spatial parameters. In someembodiments, the nanofiber arrays disclosed herein include nanofiberswhich extend from a surface of the backing member at an anglesubstantially normal to a plane containing the surface of the backingmember from which the nanofibers extend. By contrast, electrospunnanofibers, melt-blown nanofibers, and microfiber-derived nanofibers areneither integrally formed on nor do they extend from a backing member.

User-tunable physical characteristics of the nanofiber arrays disclosedherein include fiber spacing, diameter (also sometimes referred toherein as “width”), height (also sometimes referred to herein as“length”), number of fibers per unit of backing member surface area(also referred to herein as “fiber surface area density”), fibercomposition, fiber surface texture, and fiber denier. For example,nanofiber arrays used in the filter media and filter devices disclosedherein can comprise millions of nanofibers per square centimeter ofbacking member, with fiber diameter, length, spacing, composition, andtexture configured to perform a filtration function. In someembodiments, one or more of fiber surface area density, diameter,length, spacing, composition, and texture are controlled and optimizedto perform a filtration function. In certain embodiments, the nanofiberarrays can be optimized or “tuned” to perform a specific filtrationfunction or target a preselected substance or specific retentate. Infurther embodiments, an array of nanofibers disposed on a portion of afilter lamina forming a flow passage of a filter device disclosed hereinis configured to filter a substance from a fluid containing thesubstance when the fluid is flowed through the flow passage.

The nanofiber arrays disclosed herein, when formed on a substantiallyplanar surface of a backing member, can include nanofibers spaced alongan X-axis and a Y-axis at the same or different intervals along eitheraxis. In some embodiments, the nanofibers can be spaced from about 100nm to 200 μm or more apart on the X-axis and, or alternatively, theY-axis. In certain embodiments, the nanofibers can be spaced from about1 μm to about 50 μm apart on one or both of the X-axis and the Y-axis.In a preferred embodiment, the nanofibers can be spaced from about 2 μmto about 7 μm apart on one or both of the X-axis and the Y-axis.

In some embodiments, an array of nanofibers can include nanofibershaving an average length of at least 25 μm. In certain embodiments, thenanofibers can have a length of from about 10 μm to about 100 μm. Incertain embodiments, the nanofibers can have a length of from about 15μm to about 60 μm. In an exemplar embodiment, the nanofibers can have anaverage length of from about 20 μm to about 30 μm. In specificembodiments, the nanofibers can have a length of about 15.00 μm, 16.00μm, 17.00 μm, 18.00 μm, 19.00 μm, 20.00 μm, 21.00 μm, 22.00 μm, 23.00μm, 24.00 μm, 25.00 μm, 26.00 μm, 27.00 μm, 28.00 μm, 29.00 μm, 30.00μm, 31.00 μm, 32.00 μm, 33.00 μm, 34.00 μm, 35.00 μm, 36.00 μm, 37.00μm, 38.00 μm, 39.00 μm, 40.00 μm, 41.00 μm, 42.00 μm, 43.00 μm, 44.00μm, 45.00 μm, 46.00 μm, 47.00 μm, 48.00 μm, 49.00 μm, 50.00 μm, 51.00μm, 52.00 μm, 53.00 μm, 54.00 μm, 55.00 μm, 56.00 μm, 57.00 μm, 58.00μm, 59.00 μm, or 60.00 μm.

In some embodiments, an array of nanofibers can include nanofibershaving an average diameter of from about 10 nm to about 1000 nm. In anexemplar embodiment, the nanofibers can have an average diameter of 400nm to 500 nm. In certain embodiments, the nanofibers can have an averagediameter of about 10 nm, 25 nm, 50 nm, 100 nm, 150 nm, 200 nm, 250 nm,300 nm, 350 nm, 400 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, 460 nm,470 nm, 480 nm, 490 nm, 500 nm, 550 nm, 600 nm, 650 nm, 700 nm, 750 nm,800 nm, 850 nm, 900 nm, 950 nm, or 1000 nm.

The nanofiber backing member surface area density can range from about25,000,000 to about 100,000 nanofibers per cm². In some embodiments, thenanofiber surface area density can range from about 25,000,000 to about2,000,000 nanofibers per cm². In specific embodiments, the nanofibersurface density is about 6,000,000 nanofibers per cm². In an exemplarembodiment, the nanofiber surface area density is about 2,000,000nanofibers per cm².

In some embodiments, an array of nanofibers can include nanofibershaving an average denier of from about 0.001 denier to less than 1.0denier. In an exemplar embodiment, the nanofibers forming a nanofiberarray disclosed herein can be less than one denier and have a diameterranging from about 50 nm to about 1000 nm.

Nanofiber arrays and methods for producing nanofiber arrays suitable foruse in the filter media and filter devices disclosed herein aredescribed by the present inventors in U.S. 2013/0216779, U.S.2016/0222345, and White et al., Single-pulse ultrafast-laser machiningof high aspect nanoholes at the surface of SiO2, Opt. Express.16:14411-20 (2008), each of which is incorporated herein by reference inits entirety. Using the foregoing methods, nanofiber arrays with avariety of mechanical, electrical and chemical properties, Debyemoments, tailored affinities, and functional binding sites can beproduced from almost a wide variety of polymers without the use ofsolvents or high voltage electrical fields.

Nanofibers forming nanofiber arrays disclosed herein can be composed ofvirtually any thermoplastic polymer, polymer resin, or similar material.Non-limiting examples of suitable polymers include poly(ε-caprolactone)(PCL), polyethylene oxide (PEO), polyvinyl alcohol (PVA), polyvinylchloride (PVC), polyvinyl formal (PVF), polyisoprene, trans (PI),polypropylene (PP), low-density polyethylene (LDPE), high-densitypolyethylene (HDPE), PIP castline (PiPc), PIP natural (PiPn),polyvinylidene fluoride (PVDF), poly-lactic acid (PLA), andpoly-L-lactic acid (PLLA). It should be understood that a blend of twoor more such polymers can also be used. It should also be understoodthat a blend or block co-polymer of two or more such polymers can alsobe used. For example, in one embodiment, a blend of block co-polymercomprising PCL-block-PEO can be used to alter the functionality of thebacking member and nanofibers.

The term “lamina” refers to a thin modular structure having one or moresubstantially planar surfaces upon which can be formed an array ofnanofibers. Laminas of the present disclosure can take virtually anygeometric shape, including but not limited to circular, oval,rectangular, and square. In each case, the lamina will include a centralportion bounded on all sides by a peripheral portion which extendsbetween the central portion and the perimeter of the lamina. Laminas canbe formed from any suitable material which is impermeable to a fluid inneed of filtration, including the previously discussed plastics, andvarious metals and alloys, such as stainless steel.

The term “filter lamina” refers to a lamina on which is formed an arrayof nanofibers. Nanofiber arrays can be formed as an integral part of afilter lamina, or formed separately and later attached to a portion of afilter lamina by an adhesive or other means known in the art. An arrayof nanofibers can be disposed on any portion of a filter, including theupper and, or alternatively, the lower surface thereof, so that thenanofibers extend from the portion of the filter lamina. The term“spacer lamina” refers to a lamina which does not comprise an array ofnanofibers or nanoholes. Instead, a spacer lamina comprises one or moreapertures defined through a portion thereof for the purpose of formingan interlaminar space between opposing surfaces of adjacent laminas,which can be filter laminas. The terms “lamina stack” and “stack oflaminas” refers to an assembly of laminas arranged in a stackedorientation. A stack of laminas includes a top (or uppermost) lamina anda bottom (or lowermost) lamina.

The term “interlaminar space” is used herein to refer to a cavity orspace formed between opposing surfaces of adjacent laminas in a laminastack. The term “flow space” refers to a portion of an interlaminarspace through which a fluid is flowed. The term “flow passage” is usedherein to refer to a continuous passage extending through an assembly oflaminas which contains a fluid as the fluid is flowed through theassembly. For example, a flow passage is formed when an interlaminarflow space defined between two adjacent laminas is in fluidcommunication with an aperture extending through a portion of eachlamina that defines the flow space. The term “flow path” refers to thepath of fluid flow through an assembly of laminas disclosed herein.

FIGS. 1 through 5 depict a primary filter lamina 100 for a tunablenanofiber filter formed in accordance with the present disclosure, thefilter lamina 100 having a lamina thickness 102, an upper surface 104and a lower surface 106. Upper surface 104 has formed therein channels108 having a channel depth 110, a channel width 112, and a channellength, spaced a channel distance 114 apart. Channels 108 have a bottomsurface 122, a first end 116, and a second end 118. First end 116 hasformed therein apertures 120 extending from the bottom surfaces 122 ofthe channels 108 to the lower surface 106 of the filter lamina 100. Theuse of filter laminas 100 having a plurality of parallel channels 108defined therein reduces the likelihood of clogging. Filter lamina 100can be configured with locating features 130 to aid in the assembly ofmultiple filter laminas 100 into a lamina stack to form a filter of thepresent disclosure. Locating features 130 can be configured so that allupper surfaces 104 of filter laminas 100 in a filter are oriented in apredetermined direction. In some embodiments, locating features 130 canhave the same shape. In other embodiments, locating features 130 cancomprise primary and secondary locating features having differentshapes.

FIGS. 6 and 7 depict a secondary filter lamina 200 alike in all aspectsto filter lamina 100 except as specifically hereafter described.Secondary filter lamina 200 does not have channels formed in uppersurface 204.

In use, at least one primary filter lamina 100 and a secondary filterlamina 200 are positioned for assembly into a lamina stack for use in atunable nanofiber filter constructed in accordance with the presentdisclosure. For example, as shown in FIG. 8, four primary filter laminas100 and one secondary filter lamina 200 can be positioned for assemblyinto a lamina stack. Adjacent primary filter laminas 100 can be rotated180 degrees about a longitudinal axis extending through a planecontaining the laminas so that first ends 116 of channels 108 in a givenprimary filter lamina 100 are aligned with the second ends 118 of thechannels 108 in the adjacent primary filter laminas 100. In this way,the apertures 120 defined through the first ends 116 of the channels 108are in fluid communication with the second ends 118 of the channels 108of each subsequent primary filter lamina 100. Secondary filter lamina200 can be oriented and positioned on top of a lamina stack 300 as shownin FIG. 8 so that apertures 220 of secondary filter lamina 200 arealigned with the second ends 118 of channels 108 defined in the adjacentprimary filter lamina 100.

As shown in FIGS. 9 through 12, when assembled into a lamina stack 300as depicted, primary filter laminas 100 and secondary filter lamina 200of FIG. 8 form a plurality of continuous flow passages 304 extendingfrom upper surface 204 of the secondary filter lamina 200 to lowersurface 106 of the lowermost or bottom primary filter lamina 100 of thestack, the flow passages 304 being defined by apertures 120 and 220(FIGS. 11A and 11B) and by channels 108. The flow passages 304 wind liketunnels extending in alternating directions between adjacent filterlaminas through the lamina stack 300 and are bounded by the laterallyopposed (side) walls of channels 108, by the bottom surface 122 ofchannels 108, and by the lower surface 106 or 206 of the correspondingoverlying adjacent primary filter laminas 100 or secondary filter lamina200. Arrows indicate the flow path of fluid through the flow passages304 of the lamina stack 300.

FIGS. 13 through 17 depict a first (lower) portion 400 of a housing fora tunable nanofiber filter of the present disclosure. Lower housingportion 400 can have an upper planar surface 402 from which can protrudeprimary locating features 404 and secondary locating features 405configured for cooperative engagement of locating features 130 and 230of primary 100 and secondary filter laminas 200, respectively. Planarsurface 402 can have formed therein recesses 406 which form ribs 408therebetween. Ribs 408 bound trough 410 which can form a portion of aflow path in fluid communication with lumen 412 of tubular connectorportion 414 which protrudes from (lower) outer surface 416. Trough 410can have a laterally extending portion 411 configured such that whenlamina stack 300 is properly positioned on the upper planar surface 402of lower housing portion 400, apertures 120 of the bottom primary filterlamina 100 are aligned and in fluid communication with the laterallyextending portion 411 of trough 410 to allow flow therebetween. Lowerportion 400 can also have a circumferential rim 420 axially offset fromplanar surface 402.

FIGS. 18 through 22 depict a second (upper) portion 500 of a housing fora filter of the present disclosure. Upper portion 500 can have a lowerplanar surface 502 in which can be formed primary guide pin recesses 504which provide clearance for primary locating features 404 when lowerhousing portion 400 is assembled to upper housing portion 500. Planarsurface 502 can also have formed therein secondary guide pin recesses505 which can have a slightly larger but complimentary shape tosecondary locating features 405 so that when lower portion 400 isassembled to upper portion 500, cooperative engagement of secondarylocating features 405 and guide pin recesses 505 provide alignmentbetween the portions. Primary and secondary guide pin recesses 504 and505 can be the same or different shapes, but should complement theshapes of locating features 130, 230 on primary and secondary laminas100, 200, respectively. Planar surface 502 has formed therein recesses506 which form ribs 508 therebetween. Ribs 508 bound trough 510 whichforms a flow path in fluid communication with lumen 512 of tubularconnector portion 514 which protrudes from (upper) outer surface 516.Trough 510 has a laterally extending portion 511 which can be configuredsuch that when lamina stack 300 is properly positioned, apertures 220 ofthe secondary lamina 200 are aligned and in fluid communication with thelaterally extending portion 511 of trough 510 to allow flowtherebetween. Upper portion 500 can have a circumferential rim 520axially offset from lower planar surface 502.

The first (lower) housing 400 and second (upper) housing 500 portionscan be formed from one or more materials suitably impermeable to a fluidthat is to be passed through the filter, including but not limited tometals such as aluminum and stainless steel, composites such as carbonfiber, and natural or synthetic polymeric materials such as acrylics orhigh density and low density polyethylene.

In FIGS. 23 through 25, the lamina stack 300 (shown in FIGS. 9 through12) is positioned on lower housing portion 400, with the lower surface106 of the lowermost (i.e., bottom) primary filter lamina 100 resting onupper planar surface 402 of lower housing portion 400. The positioningof primary and secondary filter laminas 100 and 200 is established bycooperative action of locating features 130 and 230 of primary andsecondary filter laminas 100 and 200 with primary and secondary locatingfeatures 404 and 405 of lower housing portion 400. As best seen in FIG.25 and previously described, flow passages 304 extending back and forthbetween adjacent filter laminas from aperture to aperture down throughthe lamina stack 300 are in fluid communication with the laterallyextending portion 411 of trough 410 and therethrough to lumen 412 oflower portion 400 (see FIG. 17).

FIGS. 26 and 27 depict upper housing portion 500 positioned for assemblyto lower portion 400 and with the lamina stack 300 therein contained toform an assembled tunable nanofiber filter 600 of the presentdisclosure. Primary and secondary locating features 404 and 405 of lowerhousing portion 400 are in alignment with primary and secondary guidepin recesses 504 and 505 of upper housing portion 500. It should beunderstood, however, that in some embodiments, the position of locatingfeatures 404 and 405 and guide pin recesses 504 and 505 on the lower andupper housing portions 400 and 500, respectively, can be reversed suchthat locating features 404 and 405 protrude from the lower planarsurface 502 of the second upper housing portion 500 and the guide pinrecesses 504 and 505 are formed in the upper planar surface 402 of thefirst lower housing portion 400.

An embodiment of an assembled tunable nanofiber filter 600 of thepresent disclosure is depicted in FIGS. 28 through 31. Upper housingportion 500 can be affixed to lower housing portion 400 by the bondingof circumferential rim 420 of lower housing portion 400 tocircumferential rim 520 of upper housing portion 500. In one embodiment,the housing portions 400, 500 are bonded by ultrasonic welding. In otherembodiments, the housing portions 400, 500 are bonded by solventbonding, mechanical fastening or other joining methods known in the art.

As best shown in FIG. 31, lamina stack 300 is compressed between lowerplanar surface 502 of upper housing portion 500 and upper planar surface402 of lower housing portion 400 by ribs 508 and ribs 408, respectively.A flow path 601 (indicated by arrows) can be formed from lumen 512 oftubular connector portion 514 of the upper housing portion 500, throughtrough 510 to the laterally extending portion 511 and therefrom into thelamina stack 300 via the apertures 220 of secondary filter lamina 200,through the flow passages 304 of stack 300 as shown in FIGS. 11A and 11Band previously described, out the apertures 120 of the lowermost primaryfilter lamina 100 into the laterally extending portion 411 of trough 410of lower housing portion 400, and from trough 410 to the lumen 412 oftubular connector portion 414.

Referring now to FIGS. 32 through 34, the bottom surfaces 122 of one ormore channels 108 of the primary filter laminas 100 contained within thefilter 600 are at least partially covered with one or more arrays ofnanofibers 605. As used herein, the terms “nanofiber array” and “arrayof nanofibers” refer to a plurality of freestanding nanofibers 602extending from a backing member, the nanofibers having a predeterminednanofiber diameter 603 and nanofiber height 604 spaced at predeterminednanofiber distance 606 apart, as shown in FIGS. 32 through 34. Ananofiber array having a predetermined nanofiber diameter, height, andspacing forms a topography. Nanofiber arrays, and thus topographies, canbe tuned to suit a specific application by modulating nanofiberdiameter, height, and spacing. In some embodiments, a nanofiber arraycan be attached to a portion of a filter lamina applying an adhesivebetween the backing member of the nanofiber array and the filter laminaportion. In other embodiments, a nanofiber array can be attached to aportion of a filter lamina by using the filter lamina portion as thebacking member upon which the nanofiber array is integrally formed.

In addition, or alternatively in some embodiments, as shown in FIG. 35,a portion of the lower surfaces 106 and 206 of each primary andsecondary filter lamina 100 and 200 can be at least partially coveredwith one or more arrays of nanofibers 605. In some embodiments, theportion of the lower surfaces 106 and 206 of each primary and secondaryfilter lamina 100 and 200 overlapping a channel 108 of an adjacentunderlying primary filter lamina 100 can be include one or more arraysof nanofibers 605. For example, referring now to FIG. 35 as well asFIGS. 1 through 5, 11A, and 11B, there is depicted a portion of a flowpassage 304 of a lamina stack 300 contained in filter 600 havingnanofibers 602 formed on bottom surface 122 of channel 108 of a primaryfilter lamina 100, and on the bottom surface 106 of an adjacent primaryfilter lamina 100 overlapping the channel 108 of the underlying filterlamina 100. Opposing nanofibers 602 are separated by a nanofiber gap 608that is less than the depth 110 of channel 108. In other embodiments,the entire lower surfaces 106 and 206 of each primary and secondarylamina 100 and 200 in a lamina stack 300 can be covered with nanofibers602.

Removal of one or more contaminants from a fluid to be filtered can beaccomplished using the tunable nanofiber filter 600 by flowing the fluidinto the filter 600 via the lumen 512 in the tubular connector portion514 of the upper housing 500, through the trough 510 and the laterallyextending portion 511 thereof into the nanofiber 602 lined flow passages304 defined by the channels 108 and bottom surfaces 106, 206 of adjacentfilter laminas 100, 200 in the lamina stack 300, out of the flowpassages 304 into the laterally extending portion 411 and trough 410 ofthe lower housing portion 400, and out of the filter 600 via the lumen412 in the tubular connector portion 414 of the lower housing 400.

Once the fluid has been flowed through the flow path 601 the retentatecan be left in the filter or flushed from the filter depending on theconfiguration of nanofibers and nanoholes. The tunable nanofiber filterscan extract certain retentates from a fluid flow at different positionsalong the flow path 601 through the filter, thereby enabling extractedretentates to be used in diagnostic analyses to determine variouscharacteristics of the retentates. For example, the filter may bedisassembled and the retentate analyzed by colorimetric or other methodsto determine the composition of the retentate.

Nanofiber filters constructed in accordance with the present disclosurecan be tuned to remove specific contaminants such as pathogens, chemicalcontaminates, biological agents, and toxic or reactive compounds from afluid to be filtered by selecting one or more of nanofiber diameter 603,height 604, distance 606, gap 608, and composition to controlspecificity of filtration. For example, the height 604 of nanofibers 602and depth 110 of channels 108 can be selected to control the gap 608between opposing fibers 602 in a flow passage 304 and thus modulate theflow rate of filtrate and size of particles that can pass unhinderedthrough the gap 608.

Retentate can be retained on nanofibers by operation of local Van DerWaals forces which can be enhanced by tuning the fiber material. In someapplications, it is not necessary for the retentate to pass through thenanofibers, rather, what is necessary is merely that the retentatecontact a portion of the fibers in order to be retained. The large ratioof length of the fluid path in channels 108 to gap 608 ensures thatparticles of retentate will collide with the nanofibers 602 due todiffusion, and thus have many chances to attach to nanofibers.Electrostatic field strength is also higher at the tips of fibers sincethe tip radius curvature is always sharper than the fiber body.Attachment affinity is enhanced at the fiber tip. The gap 608 eliminatesclogging of the filter pores. Inert particles can move freely throughthe gap 608 without clogging the filter. For example, if filtering apathogen from blood, large red corpuscles could move unhindered with agap 608 of 10 microns while the nanofibers 602 capture retentate. Inthis way, filter laminas comprising arrays of freestanding nanofibers602, such as those depicted in FIGS. 32 through 34, provide a filtermedia with tunable topography that can be optimized to interact withand/or retain certain substances in unique manners in which thesubstance being affected and the character of the Debye moment and VanDer Waals interaction can be determined by the height, diameter,spacing, and constituent material of the nanofibers, as well as therelative charges of a given substance and the nanofibers.

The arrangement of nanofibers in an array can impact filtrationspecificity and efficiency by modulating the strong gradients in theelectrical and chemical potential fields of normally highly reactivesub-micron length scale structures. Control of these gradients atprocess length scales can enhance efficiency of transport or flow.However, if two nanofibers are in close proximity and the potentialfields overlap, then the gradient of the potential field is reduced andthe advantages of the nanoscale topography are reduced. The arrangementof nanofibers in a nanofiber array of the proper scale and spacing willpreserve the separation of nanofibers thus optimizing the potentialfield gradient.

The non-random placement of nanofiber tips in a nanofiber arrayrepresents a significant enhancement over nanofiber structures producedby other methods, such as electrospinning, because each fiber forming anarray of nanofibers described herein has an independent “end” or “tip.”The “ends” or “tips” of the nanofibers have stronger field gradientsthan the body of the fibers because gradients are enhanced withcurvature and the curvature is highest at the tip. Thus, the use infilter devices of nanofiber arrays having millions of tips per squarecentimeter of lamina surface preserves and enhances the local fiberfield gradient far better traditional fibrous filter media and deviceswhich rely on layered mats (woven and unwoven) of fibers laid down on asubstrate.

Accordingly, in one embodiment, the nanofiber gap 608 between ends ofopposing fibers on the bottom surface 122 of channels 108 and lowersurfaces 106, 206 of overlying filter laminas 100, 200 can be less thanabout 75% of channel depth 110. In some embodiments, the gap 608 can beless than about 50%, or less than about 30%, or even less than about 20%of channel depth 110. In certain embodiments, the gap 608 between endsof nanofibers of opposing nanofiber arrays is about 20%, 19%, 18%, 17%,16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%of channel depth 110. Opposing nanofibers 602 within a flow passage 304need not be of the same height 604, however, use of nanofiber arrays 605comprising nanofibers 602 having the same average height 604 providemore thorough, reliable, and consistent filtration by maintainingsubstantially uniform flexibility and fiber surface area. For example,the use of opposing arrays of nanofibers having a substantially uniformheight can maintain consistent filtration by both arrays, whereas theuse of opposing arrays having different average nanofiber heights canalter the filtration characteristics of the arrays in such a way thatone array filters one or more different contaminants from a fluid flowedbetween the arrays that does the other opposing array of a differentheight. Additionally, depending on the relevant characteristics of thecontaminant(s) contained in the fluid to be filtered and the relativeheights of the opposing nanofibers, one nanofiber array can become fullof a contaminant and cease contributing to filtration of the fluidbefore the other opposing nanofiber array.

Other factors which can affect the filtration characteristics of tunablenanofiber filters disclosed herein include the dimensions of channels108 formed in filter laminas. Channel dimensions can be varied toaccommodate the technical demands of any given fluid application basedon, for example, such considerations as mass and volume flow rates,viscosity, and other aspects of a given fluid which affect its flow.Although a range of exemplar channel dimensions believed to bepractically applicable to a wide variety of applications are providedherein, it should be understood that no upper limit on any suchdimensions exists or is hereby implied. For example, channel width 112and channel length can be 1.0 meter or more. However, as channel width112 increases, the rigidity of the constituent material of the laminascan begin to affect the uniformity of channel depth by permitting aportion of an adjacent overlying lamina to sag into the channel 108. Insuch cases, support structures can be positioned on the bottom surface122 of the channels 108 (for example, as shown in FIG. 44) as needed tomaintain a uniform channel depth.

Accordingly, in some embodiments, filter lamina channels 108 can have achannel depth 110 of from about 20 μm to about 1.0 cm, a channel width112 of from about 20 μm to about 2.0 mm, a channel length of from about1.0 mm to about 10 cm, and a channel distance 114 of about 10 μm toabout 500 μm. In other embodiments, filter lamina channels 108 can havea channel depth 110 of from about 20 μm to about 500 μm, a channel width112 of from about 20 μm to about 2.0 mm, a channel length of from about1.0 mm to about 10 cm, and a channel distance 114 of about 50 μm toabout 200 μm. In one embodiment, the filter lamina channels 108 can havea channel depth 110 of about 100 μm, a channel width 112 of about 200μm, a channel length of about 10 mm, and a channel distance 114 of about100 μm.

It should be noted that channel depth 110 can impact the efficiency offiltration in some embodiments of the tunable nanofiber filtersdisclosed herein. For example, increasing channel depth 110 can increasethe Reynolds Number to the point that inertial forces create turbulenceand enhance mixing. The resulting increase in flow vorticitycorrespondingly increases the probability that a particle of retentatewill contact a nanofiber disposed in the channel and thus the frequencyof surface adsorption of such particles by the nanofibers. In this way,the efficiency of filtration can be increased as a function of channeldepth 110 up to a channel depth 110 of about 5.0 cm.

In some embodiments of the tunable nanofiber filters disclosed herein,increases in efficiency of filtration can be realized based on placementand arrangement of nanofiber arrays within channels 108. For example,opposing arrays of nanofibers individually attached to the bottomsurface 122 of channels 108 and lower surfaces 106, 206 of overlyingfilter laminas 100, 200 are in the fluid boundary layer. Thearrangement, stiffness, spacing and height of the nanofibers thereforeeffect the properties of the boundary layer in the longitudinal andtransverse directions, and alter the flow profile in a complex manner.The use of nanofiber arrays to form asymmetric, opposing boundary layerprofiles can create shear stress in the channel, disrupt laminar flow,and enhance vorticity and mixing as discussed above to provide increasesin filtration efficiency. By contrast, mixing can be inhibited by narrowor shallow channels at low Reynolds Numbers where flow becomes laminarwith established boundary layers.

The primary advantage to a system in which a fluid to be filtered flowsover one or more arrays of nanofibers versus a system in which the fluidflows through the nanofibers is that “flowover” system can be designedto prevent clogging. In an engineering sense, “flowthrough” systemsapply pressure across a membrane to force fluid through the membrane.When the membrane clogs the resistance increases, requiring more workfor diminishing flow. The work required to move fluid in the presentflowover design is simply the force required to overcome viscous drag ina microchannel. This drag and thus the pressure/flow relationship willnot change over the life of the filter. Rententate or contaminates stickto nanofibers and cannot block the gap 608.

FIGS. 36 through 40 depict another primary filter lamina 700 for analternate embodiment of a tunable nanofiber filter of the presentdisclosure. Primary filter lamina 700 is identical to primary filterlamina 100 in all aspects of form and function except as subsequentlyspecifically described.

For example, filter lamina 700 has a lamina thickness 702, a first(upper) planar surface 704, a second (lower) planar surface 706, a firstend 716, and a second end 718. Filter lamina 700 also has locatingfeatures 730 which are alike in form and function to locating features130 of filter lamina 100. However, upper planar surface 704 of filterlamina 700 does not contain the channels 108 present in upper surface104 of filter lamina 100. Rather, primary filter lamina 700 has formedon upper planar surface 704 a plurality of protrusions 740 of protrusionheight 742 and protrusion diameter 744 which can be regularlygeometrically spaced a protrusion distance 746 from each other to covera central region of upper planar surface 704. Primary filter lamina 700has a single aperture 720 defined in first end 716 rather than themultiple apertures 120 of filter lamina 100. In some embodiments, thesingle aperture 720 of filter lamina 700 can be a slot.

A spacer lamina 800 which functions as a spacer and sealer layer for analternate embodiment of a tunable nanofiber filter is depicted in FIGS.41 and 42. Spacer lamina 800 of spacer lamina thickness 802 equal toprotrusion height 742 of protrusions 740 of filter lamina 700 can beformed from a variety of materials, including any suitable low-meltpolymeric material. Locating features 830 are alike in form and functionto locating features 130 of filter lamina 100. Spacer lamina 800 alsoincludes a large central aperture 850 configured such that when spacerlamina 800 and primary filter primary 700 are aligned in a stack,aperture 720 and protrusions 740 of primary lamina 700 are circumscribedby large central aperture 850 of spacer lamina 800.

FIG. 43 depicts a secondary filter lamina 900 for an alternateembodiment of a tunable nanofiber filter, secondary filter lamina 900being identical in all aspects to primary filer lamina 700 except thatupper planar surface 904 of secondary filter lamina 900 does not includethe protrusions 740 present on upper planar surface 704 of primaryfilter lamina 700. Secondary filter lamina 900 has a lower planarsurface 906 (not shown) opposite upper planar surface 904.

Laminas 700, 800 and 900 can be assembled into a stack 1000 as depictedin FIG. 44. Spacer laminas 800 are positioned between adjacent primaryfilter laminas 700, and between the uppermost primary filter lamina 700and the secondary filter lamina 900 positioned on top of the stack 1000.Adjacent primary filter laminas 700 (separated only by spacer laminas)can be rotated 180 degrees about a vertical axis extending through thestack 1000 such that the first end 716 of a given primary filter laminais aligned with and proximal to the second end 718 of any adjacentprimary filter lamina 700. Secondary filter lamina 900 can be similarlypositioned such that second end 918 of filter lamina 900 overlaps and isproximal to the first end 716 of the adjacent underlying primary filterlamina 700.

Referring now to FIGS. 45 through 47, there is depicted an assembledstack 1000 of the laminas shown in FIG. 44. As best seen in FIG. 47,aperture 920 of secondary filter lamina 900, apertures 720 of primaryfilter laminas 700, and apertures 850 of spacer laminas 800 togetherform a continuous flow passage 1001 winding in alternating directionsback and forth through the stack 1000 from the aperture 920 of thesecondary filter lamina 900 to the aperture 720 of the lowermost(bottom) primary filter lamina 700 as indicated by the arrows. Theprotrusions 740 of primary filter laminas 700 extend through the centralaperture 850 of each spacer lamina to maintain substantially uniformspacing between upper planar surfaces 704 of underlying primary filterlaminas 700 and adjacent lower planar surfaces 706, 906 of overlyingprimary filter laminas 700 and the secondary filter lamina 900,respectively, so as to permit flow of fluid through a flow space definedtherebetween and around protrusions 740 extending through aperture 850of each secondary lamina 800. The laminas of stack 1000 can be bondedtogether in a suitable fixture prior to assembly in a housing aspreviously herein described.

Upper 704 and lower 706 planar surfaces of primary filter laminas 700can have formed thereon arrays of nanofibers as previously hereindescribed and depicted in FIGS. 32 through 34. The height 742 ofprotrusions 740 of primary filter laminas 700, and the thickness 802 ofspacer laminas 800 together with the height and spacing of thenanofibers, can be chosen or “tuned” to selectively determine thefiltering characteristics of the assembled stack 1000.

The filtering characteristics of a tunable nanofiber filter device ofthe present disclosure can be configured to suit a specific intended useby changing various characteristics of the nanofibers forming a givennanofiber array, such as length, pattern or density, or by applying areactant material onto the nanofibers using printing, sputtering,chemical vapor deposition, or by the choice of the fiber compositionitself. The ability to tailor the nanofibers in these ways allows forthe creation of customized arrays of nanofibers having specificallytuned topographies which can provide multiple functions based on thedifferent diffusion and reactant rates of a fluid or fluids to befiltered when the fluid or multiple fluids to be filtered are exposed tothe nanofiber arrays. For example, whole blood is a complex fluidcontaining many chemokines, signaling molecules, leucocytes,lipoproteins, immunoglobulins. Some constituents can be filtered bysize, some by chemistry. There are a considerable number of antibodiesdesigned to bind to specific proteins, which, incorporated in the fibersin specific areas, channels or layers could separate many constituentsin one device. The specificity of filtration can be further affected bymodulating the spacing between primary filter laminas in the flow paththrough a stack of lamina (i.e., the distance between the upper andlower planar surfaces of two laminas forming the bottom and top walls ofa flow path through a lamina stack). Nonetheless, some types of fluidscan be more readily filtered using the tunable nanofiber filters of thepresent disclosure than other fluids. For example, fluids of relativelylow viscosity can be more easily filtered than fluids having relativelyhigh viscosity because with higher viscosity fluids, the nanofibers canfunction as a boundary layer which effectively decreases filtration offluid passing through and over the nanofibers.

In the exemplar embodiments of tunable nanofibers filters previouslydescribed, the nanofibers on each filter lamina have a substantiallyuniform spacing and height. In other embodiments the nanofibers on afilter lamina may be formed in discreet regions in which the height,spacing, or height and spacing the fibers within each region areconfigured (i.e., tuned) to accomplish one or more specific tasks. Forinstance, it may be desirable in certain regions to form a flow passagewith nanofibers configured to allow fluids to move therethrough withdecreased velocity so as to allow for the occurrence of out-gassing froma chemical reaction. In another instance, a different specificconfiguration of nanofibers may be required to better induce a fluid tomix in a specific manner so as to control not only a chemical reactionbut also the evolution of heat during the process.

Accordingly, FIG. 48 depicts a filter lamina 1110 having a top planarsurface with three discreet regions of nanofibers, each having its ownunique tuned topography configured for a specific function. First region1114 has nanofibers of a first height, region 1116 has nanofibers of asecond height, and region 1118 has nanofibers of a third height. Whilethe spacing between the nanofibers of the three regions is constant onfilter lamina 1110, in other configurations the spacing between thefibers may be varied by region. In still other configurations, theheight of nanofibers within a region is not constant but rather isvaried in a predetermined manner to allow tuning of the region for aspecific task. While nanofibers are shown on the top surface of filterlamina 1110 only, it will be understood that nanofibers may be formed onthe bottom surface as well so that the tuning of a specific portion ofthe flow passage is determined by the nanofibers on the top and bottomsurfaces of adjacent filter laminas, and by the spacing between thefilter laminas.

FIG. 49 depicts another filter lamina 1120 having three regions oftopology. First region 1124 has an array of nanofibers 1122 of apredetermined height, second region 1126 has no nanofibers, and thirdregion 1128 has an array of nanofibers of predetermined height. Althoughthe nanofibers of the first and third regions 1124, 1128 are depicted ashaving the same predetermined height, it will be understood that thenanofibers 1122 of the first region 1124 may having a different heightthan the nanofibers of the third region 1128.

In yet another filter lamina 1130 depicted in FIG. 50, regions 1134 and1139 each comprise an array of nanofibers having a different tunedconfiguration, and are separated by region 1136 which has no nanofibers.Instead, region 1136 comprises region 1137 in which is formed an arrayof nanoholes 1138. These nanoholes 1138 may allow certain fluids, suchas a gas, to pass vertically through layers of lamina in the assembledstack, acting as a molecular sieve. The incorporation of arrays ofnanoholes 1137 into laminas for a filter disclosed herein provides asecondary filtration path for the removal of target molecules orparticles (such as harmful gases or other undesired material) from theprimary flow passage 1001. The configuration of nanofiber arrays 1134and 1139 adjacent to the region 1137 of nanoholes (upstream anddownstream) and the configuration of the nanofiber arrays on the flowpassage wall opposite to (i.e., above) region 1137 may be optimized(i.e., tuned) to separate a specific component or contaminant from fluidfollowing the primary flow path through the primary flow passage.

FIG. 51 depicts a portion 1140 of a primary flow passage formed betweenadjacent filter laminas 1142 and 1143. Upper filter lamina 1142 andlower filter lamina 1143 are depicted with arrays of nanofibers 1144 ononly a single side of each, however this is for illustration of the flowpassage only. It will be understood that filter laminas 1142 and 1143can each have nanofibers 1144 on their opposed second surface, thenanofibers either symmetrically matching those protruding from theirfirst surface, or having different configurations. The distance 1148between adjacent surfaces of the upper and lower filter laminas 1142,1143 is constant and together with the height of nanofibers 1144 in agiven region determines the tuning and the resulting function (i.e.,filtration specificity) of that region. Flow passage portion 1140 hasfirst and second regions, 1145 and 1146 respectively, in which thedifferent heights of the nanofibers 1144 in each region creates a gap offirst and second widths between the opposing ends of the fibers in theflow path 1149, and a third region 1147 in which the height ofnanofibers on either lamina is equal to about half the space betweenadjacent surfaces of filter laminas 1142, 1143 such that no space existsbetween opposing nanofibers extending from either filter lamina 1142 or1143. In this embodiment shown, the nanofibers 1144 extending downwardfrom the lower surface of filter lamina 1142 and upward from the uppersurface of filter lamina 1143 are symmetrically opposed. In otherinstances the nanofibers are asymmetrically opposed on the filter laminasurfaces.

Another example of a partial flow passage 1150 formed by the bottomsurface of filter lamina 1152 and top surface of filter lamina 1154 isdepicted in FIGS. 52 through 56. Nanofibers 1156 of various heightscover specific regions of the opposed surfaces of filter laminas 1152and 1154 which are separated by distance 1158. Filter lamina 1154 hasformed therein a region with an array of nanoholes 1160. In a firstportion of flow passage 1150 depicted in FIG. 53, nanofibers 1156 aresymmetrically opposed between the top and bottom surfaces of filterlaminas 1154 and 1152, respectively. The tips of nanofibers 1156 on eachfilter lamina are spaced evenly from the tips of opposing nanofibers onthe other filter lamina. In a second portion of flow passage 1150 shownin FIG. 54, nanofibers 1156 extend from the bottom surface of filterlamina 1152, while the opposed upper surface region of filter lamina1152 has an absence of fibers. In a third portion of flow passage 1150shown in FIG. 55, the top surface of the flow passage has formed thereonan array of nanofibers 1156 and the bottom surface of the flow passage(i.e., the upper surface of the bottom lamina) has formed therein anarray of nanoholes 1160 configured to remove a predetermined componentfrom a fluid to be filtered passing through the primary flow path and tooutflow such predetermined component from the filter via a secondaryflow path through segregated passages therein. FIG. 56 depicts a fourthportion of the flow passage 1150 in which symmetrically opposed regionsof nanofibers 1156 are arranged with no space between the ends of theopposed fibers.

The arrangement and configurations of nanofibers, nanoholes and flowpassages in the exemplar filter laminas depicted in FIGS. 48 through 56are illustrative of variations possible within the scope of the presentinvention and are by no means the only configurations possible oranticipated. A tunable nanofiber filter formed from filter laminascomprising nanofibers and, optionally, nanoholes as disclosed herein canincorporate additional or varied features and topographies not hereindepicted and still fall within the scope of this invention. Any devicefor filtering or separating one or more substances from another liquidor gaseous substance, and which incorporates flow passages formed bylayered laminas comprising tunable topographies of nanofibers,nanoholes, or both, falls within the scope of this invention.

In the exemplar filter laminas depicted in FIGS. 48 through 56, discreetregions within a given lamina are specifically configured to filter orseparate certain substances such that a filter formed of these laminasmay perform multiple filtration and separation functions simultaneously.In other embodiments a filter can be formed having laminas of two ormore configurations combined in a lamina stack so that the filter manyselectively remove two or more components from a liquid to be filteredthat is passed through the flow passages. The laminas may each beconfigured for a single function (e.g., with a single uniform array ofnanofibers tuned to selectively filter a predetermined component from aliquid to be filtered) or may have other or additional features, such asthose filter laminas depicted in FIGS. 48 through 56.

FIG. 57 depicts a subassembly 1300 of laminas comprising tertiary andquaternary filter laminas 1302, 1322, respectively, and secondary andtertiary spacer laminas 1312, 1342, respectively, any of which caninclude surfaces on and in which are formed a tuned topography ofnanofibers and nanoholes. When combined together into an assembledsubassembly 1300, these laminas form a primary flow path (indicated withsolid arrows) and a secondary flow path (indicated with dashed arrows).The primary flow path selectively filters a fluid to be filtered bypassing the fluid through one or more regions of nanofibers having apredetermined topology as previously herein described. The secondaryflow path removes components from the fluid that are small enough topass out of the primary flow path via one or more regions of nanoholes1330 in one or more laminas.

The uppermost lamina in the subassembly 1300 is tertiary filter lamina1302, which can have formed on its lower surface an array of nanofibersof predetermined length, diameter, and spacing as previously disclosedherein. Near one end of tertiary filter lamina 1302 can be an aperture1304 that forms a portion of the primary flow path. The tertiary filterlamina 1302 can also have one or more laterally opposed apertures 1306which can form a portion of the secondary flow path. Secondary spacerlamina 1312 can have a large central aperture 1314 that can form aportion of the primary flow path, and laterally opposed apertures 1316that can form a portion of the secondary flow path. Quaternary filterlamina 1322 can have a first aperture 1324 that can form a portion ofthe primary flow path, and laterally opposed apertures 1326 that canform a portion of the secondary flow path. quaternary filter lamina 1322can have formed on its top surface adjacent to aperture 1324 a region1328 covered with an array of nanofibers of a predetermined topology. Anarray of nanoholes 1330 can be formed in a central portion of quaternaryfilter lamina 1322 bounded at one end by aperture 1324 and on eitherside by lateral apertures 1326.

The portion of the primary flow path defined by the nanofiber array onthe lower surface of uppermost tertiary filter lamina 1302, the centralaperture 1314 of secondary spacer lamina 1312, and the top surface ofquaternary filter lamina 1322 (including its region of nanofibers 1328and central region of nanoholes 1330) forms a flow space with tunedtopography which selectively separates a secondary flow of predeterminedmaterials and, or alternatively, fluids, from the primary flow path viathe nanoholes 1330 in quaternary filter lamina 1322.

Tertiary spacer lamina 1342 has a first aperture 1344 which forms aportion of the primary flow path, and a large central aperture 1345which intersects the secondary flow path so as to allow components andfluids which pass through the nanoholes 1330 of quaternary filter lamina1322 to enter the secondary flow path. The lowermost lamina in thesubassembly 1300 is another tertiary filter lamina 1302 rotated 180degrees relative to and in the same plane as the uppermost primarytertiary lamina 1302 positioned at the top of the subassembly 1300 suchthat opposite ends of the uppermost tertiary filter lamina 1302 and thelowermost tertiary filter lamina 1302 overlap. The lowermost tertiaryfilter lamina 1302 forms portions of both the primary and secondary flowpaths as previously described.

In some embodiments, such as that shown in FIG. 58, the lowermosttertiary filter lamina 1302 may be the top or uppermost tertiary filterlamina 1302 of another contiguous subassembly 1300. In such embodiments,the subsequent lower laminas of the contiguous subassembly 1300 can berotated 180 degrees (in the plane of the laminas) about a longitudinalaxis extending through the stack relative to the subassembly shown inFIG. 57 so that the primary flow path 1402 and secondary flow path 1402may extend through the adjoining contiguous subassembly 1300. Eachsuccessive contiguous subassembly descending through the stack wouldsimilarly be rotated 180 degrees from the prior adjoining subassembly.In other embodiments, the lowermost tertiary filter lamina 1302 ofsubassembly 1300 is the last tertiary filter lamina 1302 in the stackand not the top or uppermost tertiary lamina 1302 of another contiguoussubassembly 1300. In such embodiments, the bottom surface of the bottomtertiary filter lamina 1302 of the subassembly 1300 can be formed withor without an array of nanofibers thereon.

FIG. 58 depicts a lower portion 1400 of a filter stack for a tunablenanofiber filter of the present disclosure. The lower portion 1400 ofthe filter stack is composed of two contiguous subassemblies 1300 andthe bottom half 1410 of a filter housing. Solid arrows 1402 indicate theprimary flow path. Dashed arrows 1404 indicate the secondary flow path.The primary flow path 1402 exits the bottom housing half 1410 via afirst outflow connector 1406. The secondary flow path 1404 exits via asecond outflow connector 1408.

FIG. 59 depicts the upper portion 1200 of a filter stack for a tunablenanofiber filter of the present disclosure. The upper portion 1200 of afilter stack is composed of top housing half 1202 with inlet connectors1203, primary spacer laminas 1204 which have a large central aperture,primary filter laminas 1206, and secondary filter laminas 1208. Primaryand secondary filter laminas 1206 and 1208 have top and bottom surfaceson which can be formed arrays of nanofibers, and an aperture at one endthrough which the primary flow path passes. Primary filter laminas 1206can have a first nanofiber array of predetermined configurationoptimized for the selective removal of a first component from a fluid tobe filtered. Secondary filter laminas 1208 can have a second nanofiberarray of predetermined configuration optimized for the selective removalof a second component from a fluid to be filtered.

It will be understood that the surface of a particular primary orsecondary filter lamina may comprise different regions of nanofibershaving different heights, spacing, and density as previously describedherein and depicted in FIGS. 48 through 52. Solid arrows 1210 indicatethe flow path through the upper stack portion 1200. Although upper stackportion 1200 is depicted as having a series of primary and secondarylaminas configured to selectively remove components from a fluid to befiltered, additional laminas with different nanofiber configurations canbe added to upper stack portion 1200 to selectively remove additionalcomponents (such as successively smaller molecules or compounds) fromthe fluid to be filtered. Upper portion 1200 of filter stack functionsin the same manner as lamina stack 900 depicted in FIG. 44.

FIG. 60 depicts an exploded view of the components of one embodiment ofa tunable nanofiber filter 1500 of the present disclosure. The filter1500 is formed of upper stack portion 1200 and lower stack portion 1400so as to combine the different filtering characteristics of the upperand lower stack portions to provide selective removal of multiplecomponents using a single device with one filtration step.

FIGS. 61 and 62 depict the assembled lamina stack positioned forassembly into upper housing half 1202 and lower housing half 1410.Inflow connectors 1203, recess 1220 in upper housing half 1202, theassembled lamina stack with inflow aperture 1510 and outflow aperture1522, primary recess 1412 in lower housing half 1410, and outflowconnector 1406 together define a primary flow path. Lateral apertures1520 in the bottom of the assembled lamina stack, secondary recess 1414in bottom housing half 1410, and outflow connector 1408 define asecondary flow path for fluids and materials separated from the primaryflow path by the nanoholes 1330 in quaternary filter lamina laminas 1322(see FIG. 57).

FIGS. 63 and 64 depict filter 1500 fully assembled. Upper housing half1202 and lower housing half 1410 can be bonded by methods known in theart, such as ultrasonic welding or another suitable bonding method.

In traditional dialysis filters, blood and dialysate are made tointerface across a membrane. However, the present inventors havedetermined that tunable topography nanofiber filters of the presentdisclosure are much more effective at forming this interface.Additionally, in certain embodiments, the arrays of nanofibers formed onfilter laminas disclosed herein may be further functionalized with oneor more coatings or other treatments so as to overcome some of thedeficiencies associated with traditional membrane exchange. Suchfunctionalization may include, but is not limited to, coating thenanofibers with one or more elements or compounds that work to clean theblood (for example, by removing sodium from the blood) prior to theinterface with the dialysate, thereby effectively increasing theefficiency of the filtration portion of the dialysis process over thatpossible using traditional dialysis systems. Accordingly, in someembodiments, a tunable nanofiber filter of the present disclosure can bea diffusion filter.

When constructing a tunable nanofiber diffusion filter as disclosedherein, it is important that a flow path be provided through thenanofiber array(s) that allows a substantial portion of the fluids toflow down stream to the lower levels of the filter so as to promote arefreshing of fluids in the portion of the filter where the fluidsinterface. This is because egress of fluid into the nanofibers isunavoidable due to the lack of chemical or pressure drivers causing thefluid(s) to exchange or refresh. Although some fluid exchange will occurnaturally, it will occur at relatively low efficiency. Accordingly,diffusion filters of the present invention have formed therein flowpaths that allow the “exposed” fluids at the interface to exchange withnew fluid constantly. Diffusion filters so constructed preventsaturation of the filter materials (for example, the nanofibers) and theresulting eventual stalling of fluids at each level or layer.

Tunable nanofiber diffusion filter of the present disclosure can havemultiple parallel blood and dialysate passages with flow normal to theplane of the laminas. The flow paths can be arranged with dialysate flowpaths positioned between blood flow paths and separated therefrom bynanofiber arrays. The cross-sectional area of the dialysate paths can bedecreased over the length of the stack of laminas forming the filtersuch that the velocity of the dialysate increases at a predeterminedrate in relation to the blood flow rate so as to achieve a desiredexposure of the blood to the dialysate.

For example, the exchange of urea per unit area is greater at the top ofthe lamina stack than the bottom. As a result, loading of the dialysateincreases as it makes its way through the stack. The communication orexchange occurs by diffusion of urea from the blood to the dialysatethrough the nanofibers. In this way, the laminas and nanofiber arraysthereon can be configured to control the interfaces. For example, in oneembodiment, a tunable nanofiber diffusion filter of the presentinvention can include a series of blood flow paths separated fromadjacent dialysate flow paths by a series of nanofiber arrays accordingto the following pattern: blood|nanofiber array|dialysate|nanofiberarray|blood|nanofiber array|dialysate|nanofiber array|blood, and so on.The rate of diffusion is a limitation relevant to the velocity of thefluids so that the average velocity of the two fluids does not outrunthe diffusion rate when divided by ½ the distance between the blood anddialysate flow paths. Construction of the filter in this manner preventsrecontamination of the blood at the lower (i.e., down stream) portion ofthe filter.

FIGS. 65 and 66 depict a primary filter lamina 2100 for an embodiment ofa tunable nanofiber diffusion filter constructed in accordance with theprinciples of this disclosure. Primary filter lamina 2100 can have anarray of nanofibers formed on at least a portion of one or both of itsplanar upper and lower surfaces. In some embodiments, the entire upperand lower planar surfaces of the primary filter lamina 2100 are coveredin nanofibers. Defined in primary filter lamina 2100 is an array ofslots comprising a plurality of first slots 2102 having a first slotwidth 2104, and second slots 2106 having a second slot width 2108 spacedapart from the first slots. In some embodiments, the second slot width2108 can be greater than the first slot width 2104. In otherembodiments, the second slot width 2108 can be equal to or less than thefirst slot width 2104. The second slots 2106 can be centrally positionedbetween first slots 2102. First and second slots 2102, 2106 can be ofsubstantially equal length. In some embodiments, the slots arerectangular. In other embodiments, the slots can have non-linear shapesincluding semi-circular, circular, curvilinear or any combination ofthese. In still other embodiments, each slot may comprise a series ofclosely packed smaller slot or apertures of different shapes and sizes.

FIGS. 67 and 68 depict a spacer lamina 2200 for a tunable nanofiberdiffusion filter of the present disclosure. Spacer lamina 2200 has alarge central aperture 2202 which conforms closely to the outerperimeter of the array of slots formed by first slots 2102 and secondslots 2106 of filter lamina 2100.

A first lamina assembly 2300 formed of primary filter laminas 2100 andspacer laminas 2200 is depicted in FIGS. 69 through 71. First laminaassembly 2300 can be a first portion of a larger assembly of laminasforming an embodiment of a tunable nanofiber dialysis filter of thepresent disclosure. First apertures 2102 form passages for blood flow2310. Second apertures 2106 form passages for dialysate flow 2312. Asbest seen in FIG. 71, the interlaminar space between primary filterlaminas 2100 can form diffusion zones between the blood flow passages2310 formed of first apertures 2102 and the dialysate flow passages 2312formed of second apertures 2106. These diffusion zones can have firstblood diffusion portions 2302 adjacent to the blood flow passages 2310formed of apertures 2102, and first dialysate diffusion portions 2304adjacent to the dialysate flow passages 2312 formed of apertures 2106.As best seen in FIGS. 70 and 71, the blood and dialysate diffusion zones2302 and 2304 can be approximately equal in size and the boundary 2314formed there-between can be centered between first and second apertures2102 and 2106. In some embodiments, the velocity of dialysate flow 2312can be greater than the velocity of blood flow 2310.

Referring now to FIG. 72, there is depicted another filter lamina 2400for a tunable nanofiber diffusion filter of the present disclosure, thefilter lamina 2400, which can be a secondary filter lamina, beingidentical in all aspects to filter lamina 2100 (see FIGS. 65 and 66)except as specifically specified hereafter. Defined in secondary filterlamina 2400 can be an array of slots which can comprise a plurality offirst slots 2402 and second slots 2106. The width of first slots 2402 ofsecondary filter lamina 2400 can be substantially the same as the width2104 of first slots of primary filter lamina 2100. However, the width2408 of second slots 2406 of secondary filter lamina 2400 is less thanthe width 2108 of the second slots 2106 of primary filter lamina 2100.

FIGS. 73 and 74 depict a second lamina assembly 2500 formed of secondaryfilter laminas 2400 and spacer laminas 2200. Second lamina assembly 2500is identical in all aspects to first lamina assembly 2300 (see FIGS. 69through 71) except that secondary filter laminas 2400 replace primaryfilter laminas 2100 of first lamina assembly 2300. Because thecross-sectional area of second slots 2406 of secondary filter lamina2400 is less than the area of second slots 2106 of the filter lamina2100, the velocity of the dialysate through the passage formed therefromis inversely proportionately increased. This increase in velocitydecreases the distance which dialysate can diffuse into the second blooddiffusion portions 2502 and second dialysate diffusion portions 2504formed between secondary filter laminas 2400.

Accordingly, as seen in the plan view of FIG. 73 and the sectional viewof FIG. 74, the second lamina assembly 2500 has second dialysatediffusion portions 2504 adjacent to the dialysate flow passages 2512that are formed of second slots 2406 of secondary lamina 2400. Thesecond dialysate diffusion portions 2504 are decreased in size relativeto the first dialysate diffusion portions 2304 of first lamina assembly2300 (FIGS. 70 and 71). As a result, the boundary 2514 between portions2502 and 2504 of the blood and dialysate diffusion zones is shifted adistance 2520 toward the dialysate flow passage 2512 from the center2516 of the region between first and second slots 2402 and 2406. Thus,the diffusion zone boundary 2514 of second lamina assembly 2500 iscloser to the dialysate flow passage 2512 and further from the bloodflow passage 2510 than is the diffusion zone boundary 2314 of firstlamina assembly 2300.

FIG. 75 depicts a yet another filter lamina 2600, which can be atertiary filter lamina, for a tunable nanofiber diffusion filter of thepresent disclosure, the tertiary filter lamina 2600 being identical inall aspects to secondary lamina 2400 except as specifically specifiedhereafter. Defined in tertiary lamina 2600 is an array of slotscomprised of a plurality of first slots 2602 and second slots 2606. Thewidth of first slots 2602 of tertiary lamina 2600 is substantially thesame as the width of first slots of secondary lamina 2400. However, thewidth 2608 of second slots 2606 of tertiary lamina 2600 is less than thewidth 2408 of the second slots 2406 (see FIG. 72) of secondary lamina2400.

FIGS. 76 and 77 depict a third lamina assembly 2700 formed of tertiarylaminas 2600 and spacer laminas 2200. Third lamina assembly 2700 isidentical in all aspects to second lamina assembly 2500 (FIGS. 73 and74) except that tertiary laminas 2600 replace secondary laminas 2400 ofsecond lamina assembly 2500. Because the cross-sectional area of secondslots 2606 of tertiary lamina 2600 is less than the area of second slots2406 of secondary lamina 2400, the velocity of the dialysate through thepassage formed therefrom is inversely proportionately further increased.This increase in velocity further decreases the distance which dialysatecan diffuse into the third blood diffusion portions 2702 and thirddialysate diffusion portions 2704 formed between tertiary laminas 2600.

Accordingly, as seen in the plan view of FIG. 76 and the sectional viewof FIG. 77, the third lamina assembly 2700 has third dialysate diffusionportions 2704 adjacent to the dialysate flow passages 2712 that areformed of second slots 2606 of tertiary lamina 2600. The third dialysatediffusion portions 2704 are decreased in size relative to seconddialysate diffusion portions 2504 of second lamina assembly 2500 (FIGS.73 and 74). As a result, the boundary 2714 between portions 2702 and2704 of the blood and dialysate diffusion zones is shifted distance 2720toward the dialysate flow passage 2712 from the center 2716 of theregion between first and second slots 2602 and 2606 of the tertiarylamina 2600. Notably, distance 2720 of the third lamina assembly 2700 isgreater than distance 2520 of the second lamina assembly 2500. Thus, thediffusion zone boundary 2714 of third lamina assembly 2700 is closer tothe dialysate flow passage 2712 and further from the blood flow passage2710 than is the diffusion zone boundary 2514 of the second laminaassembly 2500.

A tunable nanofiber diffusion filter 2800 of the present disclosure canbe formed from multiple lamina assemblies, for example, by combiningfirst, second and third lamina assemblies 2300, 2500 and 2700 togetherto form a lamina stack as depicted in FIG. 78. First stack portion 2830can be formed of multiple first lamina assemblies 2300, second stackportion 2832 of multiple second lamina assemblies 2500; and third stackportion 2834 of multiple third lamina assemblies 2700. Once assembled,the lamina stack can be sandwiched together and contained within afilter housing comprised of a top housing portion 2802 and a bottomhousing portion 2812. The two filter housing portions can be sealedtogether using any of the methods specifically described herein orotherwise known in the art.

In use, blood 2842 enters diffusion filter 2800 via a blood inlet 2804of top housing portion 2802 and can be distributed by channels withintop portion 2802 to first slots 2102 in primary filter laminas 2100 ofthe topmost first lamina assembly 2300 (FIGS. 69 to 71) and therethroughto underlying downstream first lamina assemblies 2300 which make upfirst stack portion 2830. Blood 2842 then flows through multiple secondlamina assemblies 2500 which comprise second stack portion 2832, andsubsequently through multiple third lamina assemblies 2700 which formthird stack portion 2834. Blood 2842 exiting the bottommost third laminaassembly 2700 of third stack portion 2834 can be collected by channelswithin bottom housing portion 2812 prior to exiting the diffusion filter2800 via blood outlet 2814.

Dialysate 2844 enters diffusion filter 2800 via dialysate inlet 2806 oftop housing portion 2802 and can be distributed by channels within topportion 2802 to second slots 2106 in the topmost first lamina assembly2300 (FIGS. 69 to 71) and therethrough to underlying downstream firstlamina assemblies 2300 which make up first stack portion 2830.Therefrom, dialysate 2844 flows through multiple second laminaassemblies 2500 which make up second stack portion 2832, andsubsequently through multiple third lamina assemblies 2700 which formthird stack portion 2834. Dialysate 2844 exiting the bottommost thirdlamina assembly 2700 of third stack portion 2834 can be collected bychannels within bottom housing portion 2812 prior to exiting thediffusion filter 2800 via dialysate outlet 2816.

Referring again to FIG. 78, the length of arrows indicating blood flow2842 and dialysate flow 2844 through diffusion filter 2800 correspond tothe relative velocities of the indicated flows at different positions inthe filter. The velocity of blood flow 2842 through filter 2800 isconstant, whereas the velocity of dialysate flow 2844 is incrementallyincreased as the dialysate flow 2844 proceeds through first, second, andthird stack portions 2830, 2832 and 2834 of filter 2800 in order toaccomplish the objectives previously herein described.

The lamina stack of diffusion filter 2800 of the illustrative andnon-limiting example depicted in FIG. 78 has three lamina configurationswhich create two incremental increases in the velocity of dialysate flow2844 in order to illustrate the principles of increased dialysate flow2844 and the related effect on the diffusion zones. The number of laminaconfigurations and the resulting number of incremental flow velocityincreases is a design choice and may be optimized to achieve desiredresults or to suit a particular application. Some embodiments may haveincreasing downstream dialysate flow velocities, or alternativelyreduced downstream blood flow rates, or a combination of the two. Flowvelocity may be modulated by modifying the cross-sectional area of theappropriate flow passages. Accordingly, any filter having parallelinterspersed, blood and dialysate flow passages which are separated by adiffusion zone formed of opposed arrays of freestanding nanofibers fallswithin the scope of this disclosure.

Blood 2842 entering diffusion filter 2800 typically will haveundesirably high concentrations of solutes such as urea, potassium andphosphorus. Dialysate 2844 has low concentrations of such solutes. As aresult, and with reference to FIGS. 70 and 71, such solutes flow fromblood 2842 through first blood diffusion zone 2302 to first dialysatediffusion zone 2304 and therethrough to dialysate 2844, and aretransported thereby downstream and out of the filter 2800. Because theconcentrations of the targeted solutes increases in the dialysate flowstream as it progresses through filter 2800, the rate of diffusion fromblood 2842 to dialysate 2844 will decrease unless the flow rate ofdialysate 2844 is increased commensurately. If the flow rate of thedialysate 2844 is not increased in these downstream portions, theconcentration of the targeted solutes in the dialysate 2844 can approachthe concentrations of these solutes in the blood 2842, in which casediffusion of these solutes from blood to dialysate will decreaseproportionately. In an extreme case, wherein the flow rate of thedialysate 2844 in the downstream portions of the diffusion filter 2800is not increased, the concentration of targeted solutes in the dialysate2844 may exceed those of the “cleaned” blood 2842 and diffusion of thetargeted solutes may be reversed thereby undesirably increasing levelsof the targeted solutes in the blood. Accordingly, the relative flowrates of blood 2842 and dialysate 2844 through diffusion filters of thepresent disclosure should not be constant but rather should be modifiedso as to maintain optimal diffusion rates of solutes through thenanofiber diffusion zones in all portions of the filter 2800.

In this way, a tunable nanofiber diffusion filter of the presentdisclosure is analogous to a metro transfer point in which red linetrains represent blood flow, green line trains represent dialysate flow,and passengers represent solute. Passengers wishing to transfer from thered line to the green line need few trains if the arriving green linecars are empty. As the amount of space on arriving green line carsdecreases, the number of arriving green line cars required to transportthe arriving red line passengers must be increased. If there is no spaceon the arriving green line cars, the transport of arriving red linepassengers ceases. Optimal transfer of arriving red line passengers todeparting green line trains is achieved by ensuring that available spaceon the arriving green line cars always substantially exceeds thatrequired for arriving red line passengers wishing to transfer.Accordingly, filters of the present invention can be configured suchthat the relative flow rates and solute concentrations of the blood anddialysate are optimized for solute diffusion from the blood to thedialysate in all portions of the filter.

In the previous illustrative example, diffusion filter 2800 is describedwith reference to blood 2842 and dialysate 2844. This choice is forexample only and should not be construed as limiting upon the types offluids that may be cleaned using a tunable nanofiber filter disclosedherein. In practice first fluid 2842 and second fluid 2844 may compriseany fluid combination in which first fluid 2842 is filtered by diffusionof materials therefrom to a second fluid 2844 by means of one or morediffusion zones comprising nanofibers.

Referring again to diffusion filter 2800, the dense nanofiber arrayforms an interface or boundary 2314 across which blood 2842 anddialysate 2844 do not typically directly interact and only solutemolecules pass. Referring again to FIG. 71, blood 2842 penetrates thenanofiber array formed on the top and bottom surfaces of filter lamina2100 to fill blood diffusion zones 2302. In the same manner, dialysate2844 penetrates the nanofiber array to fill dialysate diffusion zones2304. At the boundary of diffusion zones 2302 and 2304 (i.e., lines2314), solute molecules pass from blood 2842 to dialysate 2844.

However, as indicated by the laterally extending arrows, blood 2842 anddialysate 2844 flow readily into the blood and dialysate diffusionzones, 2302 and 2304, respectively. A significant portion of the fluidmay remain stalled (stagnant) within the diffusion zones such that afteran initial solute exchange from blood 2842 to dialysate 2844, diffusionacross the interface or boundary 2314 may cease because the soluteconcentration of the local dialysate 2844 has reached equality with thatof the local blood 2842. So long as the blood 2842 and dialysate 2844remain stagnant, no further diffusion can occur. Some exchange of thefluids may occur, but such exchange will be inefficient and limit theeffectiveness of filter 2800.

To eliminate this condition it is necessary that there be flow withinthe diffusion zones with the flow having a component parallel to firstand second slots 2102 and 2106 of primary filter lamina 2100, and to theboundary 2314 between blood and dialysate diffusion zones 2302 and 2304,respectively, so as to refresh the fluids in the zones. Accordingly, inanother embodiment a flow path is created within the nanofiber arraywhich allows a portion of the fluids within the nanofiber array to flowto the lower levels of the lamina stack so as to promote refreshing ofthe fluids within the array at the boundary and diffusion zones. Theflow path is created for the “exposed” fluids at the interface toexchange with new fluids constantly so as to prevent stalling of fluidswithin the diffusion zones and resulting saturation of the filter.

FIG. 79 depicts another embodiment of a primary filter lamina 3100 for atunable nanofiber diffusion filter, the filter lamina 3100 beingidentical to primary filter lamina 2100 (FIGS. 65 and 66) in all aspectsexcept as specifically described hereafter. Filter lamina 3100 hasformed therein first apertures 3103 in proximity to first slots 3102,and second apertures 3107 in proximity to second slots 3106. Filterlamina 3100 is formed with parallel linear first and second slots 3102and 3106 for primary blood and dialysate flow, and first and secondapertures 3103 and 3107 for secondary blood and dialysate flow to creategradients within the diffusion zones. First and second apertures 3103and 3107 are positioned in proximity to the lateral ends of the firstand second slots 3102 and 3106, respectively.

The positioning of primary blood and dialysate flow passages and theirassociated secondary flow passages is a design choice, as is their sizeand configuration. The size, configuration and positioning of thesefeatures may be optimized to meet certain specific requirements withregard to size, flow rate, back pressures, or other requirements. Forexample, the slots may have non-linear shapes including semi-circular,circular, curvilinear or any combination of these. Similarly, theapertures for secondary flow (i.e., first and second apertures 3103 and3107) may also have a variety of shapes including circular, oblong,rectilinear, or any combination of these shapes. Any diffusion filterwhich has parallel primary flow paths for blood and dialysate, adjacentdiffusion zones which meet at an interface and comprise a nanofiberarray, and one or more secondary flow paths which intersect one or moreof these diffusion zones for the purpose of creating flow within thediffusion zone in proximity to the interface, falls within the scope ofthis invention.

FIGS. 80 to 83 depict a lamina subassembly 3300 comprising a pluralityof filter laminas 3100 and spacer laminas 3200. Each spacer lamina 3200is identical in all regards to spacer lamina 2200 shown in FIGS. 67 and68 and described above. The dashed arrows in FIGS. 82 and 83 indicateflow within first diffusion zones 3302 adjacent to first slots 3102 andfirst apertures 3103, and flow within second diffusion zones 3304adjacent to second slots 3106 and second apertures 3107. Flow exitingfirst and second diffusion zones 3302 and 3304, respectively, isreplaced by “fresh” fluids flowing into the zones from their respectiveadjacent primary flow paths through flow passages formed by first andsecond slots, 3102 and 3106, respectively. In both cases the directionof the flow has a component parallel to the interfaces or boundariesbetween diffusion zones 3302 and 3304 so as to cause a refreshing of thefluids in the respective zones adjacent to their interface.

Referring now to FIG. 83, primary blood flow 3310 flows through flowpassages formed by first slots 3102 downward through lamina subassembly3300. Primary dialysate flow 3312 flows through flow passages formed bysecond slots 3106 downward through first lamina subassembly 3300.Secondary blood flow 3311 flows through flow passages formed by firstapertures 3103 downward through lamina subassembly 3300, with the volumeof blood flow increasing with the addition of blood from downstreamfirst diffusion zones 3302 (FIG. 82). Secondary dialysate flow 3313flows through flow passages formed by second apertures 3107 downwardthrough lamina subassembly 3300, with the volume of dialysate flowincreasing with the addition of dialysate from downstream seconddiffusion zones 3304 (FIG. 82). To accommodate this increased flow, thesizes of first and second apertures 3103 and 3107 in downstream primarylaminas 3100 of lamina subassembly 3300 are incrementally increased withincreasing distance from the uppermost lamina in the lamina subassembly3300.

FIG. 84 depicts a lamina stack and bottom portion of a filter housingfor an embodiment of a tunable nanofiber diffusion filter 4000 formed inaccordance with the present disclosure. The lamina stack comprises anupper stack portion 4002 including a quaternary filter filter lamina4100 overlying the lamina subassembly 3300 of FIGS. 80 through 83, and alower stack portion 4004 including multiple additional filter laminasoverlying another a quaternary filter lamina 4100.

Specifically, lower stack portion 4004 includes a secondary spacerlamina 4200, a secondary filter lamina 4400 underlying secondary spacerlamina 4200, a tertiary spacer lamina 4500 underlying secondary filterlamina 4400, a tertiary filter lamina 4600 underlying tertiary spacerlamina 4500, a quaternary spacer lamina 4700 underlying tertiary filterlamina 4600, and a quaternary filter lamina 4100 underlying tertiaryspacer lamina 4600.

Lower stack portion 4004 receives blood 4310 and dialysate 4312 fromupper stack portion 4002 through secondary spacer lamina 4200 in whichis formed slots and apertures matching those of the lowermost primaryfilter lamina 3100 of upper stack portion 4002. Secondary filter lamina4400 has openings 4460 that receive primary and secondary blood flow3310 and 3311 exiting first slots 3102 and first apertures 3103,respectively, of the lowermost primary filter lamina 3100 (see FIG. 83)in the lamina subassembly 3300 in the upper stack portion 4002 so as tocombine primary and secondary blood flow 3310, 3311 for passage throughlower stack portion 4004.

Tertiary spacer lamina 4500 has formed therein slots and aperturesmatching those of adjacent overlying secondary filter lamina 4400. Insome embodiments, tertiary spacer lamina 4500 may be thinner thansecondary filter lamina 4400. In other embodiments, tertiary spacerlamina 4500 may be of the same or greater thickness as secondary filterlamina 4400.

Tertiary filter lamina 4600 has openings 4670 which receive primary andsecondary dialysate flow streams 3312 and 3313 exiting second slots 3106and second apertures 3107, respectively, of bottom primary filter lamina3100 (see again FIG. 83) of the lamina subassembly 3300 in the upperstack portion 4002 so as to combine primary and secondary dialysate flow3312, 3313 for passage through the remainder of lower stack portion4004.

Quaternary spacer lamina 4700 has formed therein slots and aperturesthat match those of adjacent overlying tertiary filter lamina 4600.Blood 4310 and dialysate 4312 exit quaternary filter lamina 4100 and arereceived by recesses within bottom filter housing portion 4800 and flowtherethrough to blood and dialysate outflow connectors 4810 and 4812,respectively.

Referring again to FIG. 82, the flow within the diffusion zonesindicated by the dashed arrows is due to a pressure gradient created bythe presence of first and second apertures 3103 and 3107 and the flowpassages formed thereby. This flow within the diffusion zones created bythese pressure gradients causes a refreshing of fluids within eachdiffusion zone, the flow being from the primary flow passages formed byfirst and second slots 3102 and 3106, and the secondary flow passagesformed by first and second apertures 3103 and 3107. A portion of thisflow brings fresh fluid to the region within each diffusion zone that isadjacent to the interface or boundary between diffusion zones. Thisrefreshing of the fluids adjacent to the interface brings cleandialysate and “dirty” blood to the diffusion zone interface therebydiffusing predetermined solutes from the blood to the dialysate forsubsequent transport out of the filter by the dialysate flow.

Diffusion filters 2800 and 4000 previously herein described haveparallel axial flow paths for blood and dialysate, the flow paths beingsubstantially normal to the plane of the laminas. Arrays of nanofibersextending from top and bottom surfaces of the constituent laminas intothe interlaminar space function as a semipermeable membrane that passessolute from the blood to the dialysate. However, in another exemplarembodiment of the present invention hereinafter described, the dialysateflow can be axial, normal to the plane of the laminas, and the bloodflow path can take a circuitous path through the interlaminar spaces,the dialysate and blood flow paths being substantially perpendicular.

Accordingly, FIGS. 85 and 86 depict a filter lamina 5100 for anotherembodiment of a tunable nanofiber diffusion filter constructed inaccordance with the present disclosure in which the dialysate flow pathis perpendicular to the filter lamina 5100 and the blood flow pathpasses through the interlaminar space, parallel to the plane of thefilter lamina 5100.

Filter lamina 5100 has first and second longitudinal slots 5104, a thirdlongitudinal slot 5106 centrally located between first and secondlongitudinal slots 5104, and a lateral slot 5102 perpendicular tolongitudinal slots 5104, 5106. As shown in FIG. 86, filter lamina 5100has symmetrically opposed arrays of nanofibers formed on its upper andlower surfaces. First nanofiber arrays 5112 can be positioned in closeproximity to longitudinal slots 5104 and 5106 and can be formed ofnanofibers 5110 spaced a first array distance 5113 apart. Secondnanofiber arrays 5114 can be positioned adjacent to first nanofiberarrays 5112 and can be formed of nanofibers 5110 spaced a second arraydistance 5115 apart. First array distance 5113 can be between about oneand ten microns, or between about one and five microns. In someembodiments, the first array distance 5113 can be about 1, 2, 3, 4, 5,6, 7, 8, 9, or 10 μm. Second array distance 5115 is preferably greaterthan first array distance 5113, and can be between about 200 microns to2 microns. The ratio of second array distance 5115 to first arraydistance 5113 can be between about 2:1 and about 20:1, or between about4:1 and about 10:1. In some embodiments, the ratio of second arraydistance 5115 to first array distance 5113 can be about 10:1, 9:1, 8:1,7:1, 6:1, 5:1, 4:1, 3:1, or 2:1. First and second nanofiber arrays 5112and 5114 can be separated by a region 5116 having no nanofibers, asshown in FIGS. 85 through 86.

FIGS. 87 and 88 depict a spacer lamina 5200 for use with filter lamina5100 in a lamina stack for a tunable nanofiber diffusion filter of thepresent disclosure. Spacer lamina 5200 has a large central opening 5204defined by perimeter 5202.

FIGS. 89 and 90 depict filter lamina 5100 and spacer lamina 5200assembled into a portion of a lamina stack for use in an embodiment of atunable nanofiber diffusion filter of the present disclosure. Slots 5104of filter lamina 5100 are bounded on their medial sides by firstnanofiber arrays 5112, and their other (i.e., lateral) sides byperimeter 5202 of opening 5204 of spacer lamina 5200. Lateral slot 5102of filter lamina 5100 is bounded on three sides by perimeter 5202 ofopening 5204 of spacer lamina 5200.

FIG. 91 depicts an exploded view of a lamina subassembly 5300 comprisinga spacer lamina 5200 between two filter laminas 5100. Arrows indicatethe direction of dialysate flow 5302, blood flow 5304, and diffusionflow 5306. The central opening of the spacer lamina 5200 defines aninterlaminar space between adjacent overlying and underlying filterlaminas 5100. Blood 5304 flows into the interlaminar space via lateralslot 5102 in overlying filter lamina 5100, through the interlaminarspace primarily via nanofiber free regions 5116, but also through secondnanofiber arrays 5114, and to a lesser extent through first nanofiberarrays 5112. Blood 5304 exits the interlaminar space via lateral slot5102 in underlying filter lamina 5100. Dialysate 5302 flows verticallythrough lamina assembly 5300 through longitudinal slots 5104 and 5106.Blood flowing through first nanofiber arrays 5112 adjacent tolongitudinal dialysate flow slots 5104 and 5106 allows the diffusion ofselected solutes from blood 5304 to dialysate 5302.

FIG. 92 depicts an embodiment of a housing 5400 for an alternateembodiment of a tunable nanofiber diffusion filter constructed inaccordance with the present disclosure. Housing 5400 includes an upperportion 5402 having a central window 5404 and an inlet connector 5406,and a lower portion 5410 having a central window 5412 and an outletconnector 5414. The windows in the upper and lower housing portions canbe large central apertures defined through each housing portion.

FIG. 93 depicts a tunable nanofiber diffusion filter 5500 comprisinghousing 5400 and a lamina stack comprising multiple lamina subassemblies5300 formed from a plurality of filter laminas 5100 and spacer laminas5200. The nanofiber arrays depicted in FIG. 91 are omitted for clarity,but it should be understood that such nanofiber arrays or variationsthereof can be present on the surfaces of filter laminas 5100. Dialysate5502 enters filter 5500 via window 5404 in upper housing portion 5402and flows via slots 5104 and 5106 in filter laminas 5100 through filter5500, exiting via window 5412 in lower housing portion 5410. Blood 5504enters filter 5500 via inlet connector 5406 in upper housing portion5402 and follows an interlaminar path as previously herein describedwith regard to upper filter portion 1200 of filter 1500 as depicted inFIG. 59, exiting filter 5500 via outlet connector 5414.

FIGS. 94 through 96 depict filter 5500 assembled for use with upperhousing portion 5402 being permanently affixed to lower housing portion5410 in a manner which seals the laminas shown in FIG. 93 within upperand lower housing portions 5402 and 5410. Unlike previously describeddiffusion filters 2800 (FIG. 78) and 4000 (FIG. 84) which have adialysate flow path connected to an external source via tubing andconnectors, filter 5500 is configured to be submerged in dialysateduring use, as shown in FIG. 97.

Referring now to FIG. 97 depicting filter 5500 submerged in a vesselfilled with dialysate 5502, blood 5504 is supplied to filter 5500 byfirst tubular member 5802 connected to inlet connector 5406 of upperhousing portion 5402. Outflow of the filtered blood 5504 is via secondtubular member 5804 connected to outflow connector 5412 (not shown) oflower housing portion 5410. Dialysate in which the filter 5500 issubmerged can flow from the surrounding environment through slots 5104and 5106 of filter laminas 5100 as a result of natural convectioncurrents, forced fluid motion, or other means.

In use, filter 5500 and other filters of the present disclosure in whichthe path for the flow of a fluid is primarily through the interlaminarspaces parallel to the plane of the laminas, resistance to the flow mayexceed that desired for a specific application. This resistance,referred to as “back pressure,” may be reduced by modifying variousparameters of the flow path passing through the laminas. Such parametersinclude, without limitation, the distance between adjacent laminas, thedepth of lamina channels, the gap or space between opposing nanofiberarrays extending into the flow space or flow passages from adjacentlaminas, and the distance between nanofibers in an array of nanofibers.

FIGS. 98 and 99 depict another filter lamina 5600 for an alternateembodiment of the tunable nanofiber diffusion filter of FIG. 93 that issimilar in construction to filter 5500, but with decreased resistance toblood flow. Secondary filter lamina 5600 is identical to filter lamina5100 in all aspects of form and function except as specificallydescribed hereafter. Specifically, secondary filter lamina 5600 hasfirst and second longitudinal slots 5604, a third longitudinal slot 5606centrally located between first and second longitudinal slots 5604, anda lateral slot 5602 perpendicular to longitudinal slots 5104, 5106.However, secondary filter lamina 5600 also has a second lateral slot5602 disposed symmetrically opposite to first lateral slot 5602 relativeto longitudinal slots 5604, 5606, whereas filter lamina 5100 does nothave this second lateral slot.

FIG. 100 depicts a partial lamina stack 5700 for use in the decreasedresistance to blood flow embodiment of the tunable nanofiber diffusionfilter shown in FIG. 93. For clarity in depicting the interlaminar flowpaths, the spacer laminas 5200 are not shown. It will be understood thatthe construction of filter 5500 is like that of embodiments previouslyherein described (for example, the embodiment shown in FIG. 93) in thatspacer laminas 5200 are interspersed between adjacent filter laminas5100 and 5600.

As with the lamina stack of filter 5500, dialysate flow 5702 in laminastack 5700 is substantially normal to a plane containing the stackedlaminas through longitudinal slots 5104 and 5106 of filter laminas 5100,and through longitudinal slots 5604 and 5606 of secondary laminas 5600.The flow path of blood 5704 through lamina stack 5700 allows the bloodflow 5704 to divide between multiple parallel flow paths extendingthrough the interlaminar spaces.

Blood 5704 enters through slot 5102 in the uppermost filter lamina 5100and fills a flow space created by the multiple coaxially positionedlateral slots 5602 in secondary filter laminas 5600 thereunder, thebottom of the flow space being formed by the portion of filter lamina5100 which is positioned beneath the last filter lamina 5100 forming theflow space. Blood flow from the flow space is through the parallelinterlaminar spaces formed by the uppermost and middle primary filterlaminas 5100 and secondary filter laminas 5600 positioned therebetween.Blood flows from the interlaminar spaces to a flow space formed byopposite lateral slots 5602 of the secondary filter laminas 5600 andslot 5102 of filter lamina 5100 positioned in the center of the stacksegment. The top of the flow space is formed by coaxially positionedportion of the uppermost filter lamina 5100, and the bottom of the flowspace is formed by the coaxially positioned portion of the lowermostfilter lamina 5100.

Blood flows from the upper portion of the cavity through slot 5102 inthe middle filter lamina 5100 to the lower portion of the flow space.From the lower portion of the flow space the blood flows through theinterlaminar spaces formed by the middle and lowermost filter laminas5100 and by the secondary filter laminas 5600 positioned therebetween.The blood is collected in a flow space formed by the first lateral slots5602 in secondary filter laminas 5600 with the top of the flow spacebeing formed by the coaxially located portion of the middle filterlamina 5100. Blood flows downward from this flow space to an adjacentportion of the lamina stack or to an outflow connector.

It will be understood that the parallel flow path model illustrated inFIG. 100 may be applied to any filter of the present disclosure in whichone or more fluids flow through the interlaminar spaces. The number ofparallel interlaminar paths among which the flow is divided can beoptimized for specific applications, as can the number of laminas usedin the lamina stack.

Diffusion filters 2800 and 4000 previously herein described haveparallel axial flow paths for blood and dialysate that flow through thefilter in the same direction. Diffusion filters 5500 and 5700 have axialdialysate flow paths, the dialysate flow paths being substantiallynormal to the plane of the laminas, and blood flow paths which flowthrough the interlaminar spaces extending back and forth betweenadjacent laminas down through the stack. However, it can be beneficialin some instances to have a tunable nanofiber diffusion filter in whichthe blood and dialysate both flow through the interlaminar spaces, theflow paths being separated by nanofiber arrays as previously hereindescribed. Further, it can be beneficial in certain cases to have acounterflow condition between the dialysate and blood flows within theseinterlaminar spaces, the flow paths being parallel but flowing inopposite directions.

Accordingly, FIGS. 101 and 102 depict a primary filter lamina 6100 foranother embodiment of a tunable nanofiber diffusion filter constructedin accordance with the present disclosure in which blood and dialysateflow through the interlaminar space via parallel but counterflowing flowpaths. Primary filter lamina 6100 can have on its upper and lowersurfaces symmetrically opposed parallel nanofiber arrays 6102 and slots6104.

FIGS. 103 and 104 depict a spacer lamina 6200 for use with primaryfilter lamina 6100 in a lamina stack for a tunable nanofiber diffusionfilter of the present disclosure. Spacer lamina 6200 has a large centralopening 6202 defined by perimeter 6204.

FIGS. 105 and 106 depict a lamina subassembly 6300, the subassembly 6300being formed from a spacer lamina 6200 and a primary filter lamina 6100.The lamina subassembly 6300 can have a first end 6302 and a second end6304. Nanofiber arrays 6102 of primary filter lamina 6100 and perimeter6204 of opening 6202 of spacer lamina 6200 together define alternatingfirst and second channels 6120, 6122 for counterflowing blood anddialysate, with each channel 6120, 6122 having a slot 6104 at each endthereof.

FIG. 106 depicts counterflowing blood and dialysate flow paths(indicated by arrows) in the interlaminar space, which can be defined bythe central opening 6202 of the spacer lamina 6200, the bottom surfaceof an adjacent overlying primary filter lamina 6100, and the uppersurface of an adjacent underlying primary filter lamina 6100. Thedirection of flow in a given channel 6120, 6122 is determined by thepressure differential at the ends of the channel. Each channel has aninflow slot 6110 and an outflow slot 6112 positioned at its oppositeends, slots 6110 and 6112 being formed by slots 6104 of primary filterlamina 6100. First channels 6120 have inflow slots 6110 at first end6302 of the subassembly 6300. Second channels 6122, positioned betweenfirst channels 6120, have inflow slots 6110 at second end 6304 of thesubassembly 6300.

FIG. 107 depicts a secondary filter lamina 6400, which is identical inall aspects of form and function to primary filter lamina 6100 except asspecifically described herein. Notably, nanofiber arrays 6402 are formedon only one side of secondary filter lamina 6400, secondary filterlamina 6400 has fewer and slots 6404 than primary filter lamina 6100,and the slots 6404 of secondary filter lamina 6400 are not symmetricallyopposed. In some embodiments, the slots 6404 of secondary filter lamina6400 can be positioned as depicted.

FIG. 108 depicts a lamina stack 6500 for an embodiment of a tunablenanofiber diffusion filter of the present disclosure. The lamina stack6500 can be formed of two primary filter laminas 6100 (FIGS. 101 and102), three spacer laminas 6200 (FIGS. 103 and 104), and two secondaryfilter laminas 6400 (FIG. 107). Spacer laminas 6200 are not depicted forimproved clarity, but should be positioned in stack 6500 betweenadjacent filter laminas 6100, 6400 in accordance with the principlespreviously described herein. Slots 6404 of the uppermost secondaryfilter lamina 6400 align with inflow slots 6110 of the primary filterlaminas 6100 (see FIG. 106), and slots 6404 of the bottommost secondaryfilter lamina 6400 align with outflow slots 6112 of the primary filterlaminas 6100.

A first flow path is formed through the lamina stack 6500 by slots 6404in the uppermost secondary filter lamina 6400 at the first end 6502 ofthe stack 6500, together with slots 6110, channels 6120, and slots 6112of lamina subassemblies 6300, and slots 6404 in the lowermost secondaryfilter lamina 6400 at the second end 6504 of the stack 6500. A secondflow path is formed through the lamina stack 6500 by slots 6404 in theuppermost secondary filter lamina 6400 at the second end 6504 of thestack 6500, together with slots 6110, channels 6120, and slots 6112 oflamina subassemblies 6300, and slots 6404 in the lowermost secondaryfilter lamina 6400 at the first end 6502 of the stack 6500. The firstand second flow paths are parallel through the interlaminar spaces butthe flow of each is in opposite directions. Nanofiber arrays 6102, 6402between the first and second flow paths in the interlaminar space candiffuse solutes between fluids in the first flow path and the secondflow path.

In another embodiment, the nanofiber arrays 6102 on primary filterlaminas 6100 forming a first portion of the lamina stack 6500 can have afirst configuration while the nanofiber arrays 6102 on primary filterslaminas 6100 forming a second portion of a lamina stack 6500 can have asecond configuration such that a first solute can be removed from afluid passing through the first portion and a second solute can beremoved from the fluid in the second portion.

FIG. 109 depicts an embodiment of a tunable nanofiber diffusion filter6600 of the present disclosure. The filter 6600 includes the laminastack 6500 of FIG. 108 contained within housing formed from a lowerhousing portion 6602 and an upper housing portion 6612. It should benoted that the orientation of the lamina stack 6500 as it is depicted inFIG. 109 is reversed from that shown in FIG. 108 such that the first andsecond ends 6502, 6504 of the lamina stack 6500 are shown on oppositesides. It should also be noted that the lamina stack 6500 depicted inFIG. 109 includes sufficient primary filter laminas 6100 to illustratethe parallel interlaminar counterflowing flow paths, however, as manyadditional primary filter laminas 6100 can be used in the stack 6500 asmay be needed or desired to satisfy specific filtering requirements forany given application.

Filter 6600 can have a lower housing portion 6602 wherein can be formeda first recess 6604 which receives flow from slots 6404 (FIG. 108)positioned axially adjacent thereto and which conducts the flow viafirst passage 6606 to a first outflow connector (not shown). Lowerhousing portion 6602 can also have formed therein a second recess 6608which receives flow from slots 6404 positioned axially adjacent theretoand which conducts the flow via second passage 6610 to a second outflowconnector (not shown). Filter 6600 can also have an upper housingportion 6612, which can be symmetrically identical to lower housingportion 6602 and have formed therein first and second recesses forconducting flow from a first input connector 6616 to slots 6404 withwhich the first recess is axially aligned, and for conducting flow froma second input connector 6620 to slots 6404 with which the second recessis axially aligned.

First fluid 6640, the flow path of which is depicted by dashed arrows inFIG. 109, enters filter 6600 via first inflow connector 6616 andthereafter flows through the flow path indicated by dashed arrowsthrough lamina stack 6500 and then via second recess 6608 and secondpassage 6610 to a second outflow connector (not shown). Second fluid6642, the flow path of which is depicted by solid arrows in FIG. 109,enters filter 6600 via second inflow connector 6620 and thereafter flowsthrough the flow path indicated by solid arrows through lamina stack6500 and then via first recess 6604 to a first output connector (notshown). The flow of first fluid 6640 and of second fluid 6642 aresymmetrically opposite in the interlaminar spaces between adjacentfilter laminas of lamina stack 6500.

Filters of the present invention use tuned topographies of freestandingnanofiber arrays extending from portions of filter laminas to separateparticles and solutes from fluid streams passing over, across, orthrough the topographies. A filter of the present disclosure can includefilter laminas having a single topography configured to remove a singlepreselected substance, or filter laminas having two or more differenttopographies, each optimized to removed a different preselectedsubstance. Additionally, a filter lamina for a filter disclosed hereincan include a single topography tuned to remove a single preselectedsubstance, or two or more topographies on the same filter lamina, eachtopography configured to remove a different substance. In someembodiments filter laminas can also, or alternatively, include one ormore arrays of nanopores to allow outgassing of selected substances fromthe fluid stream. The unique custom configurations which may beconstructed using the principles previously herein described allowfilters of the present disclosure to accommodate a wide range of fluids,including any liquid or gas which can be passed through such a filter.

In certain embodiments, the filters disclosed herein can be diffusionfilters having one or more arrays of freestanding nanofibers that form asemi-permeable membrane which allows one or more preselected solutes todiffuse from a second fluid stream to a first fluid stream. As with theembodiments previously described, the nanofiber arrays between the flowpaths of the first and second fluid streams may have a singleconfiguration in a filter so as to remove a single solute or family ofsolutes, or may have two or more configurations so as to remove two ormore selected solutes. A variety of flow paths are anticipated. Thesemay include parallel axial flow paths for the two fluids, parallel axialcounter-flowing fluid paths, flow paths in which a first fluid flowsaxially and a second fluid flows through the interlaminar spaces betweenadjacent filter laminas, or flow paths in which both fluids flow throughthe interlaminar spaces between adjacent filter laminas. In each casethe two flow paths are separated by nanofiber arrays which allowdiffusion of one or more selected solutes from a second fluid stream toa first fluid stream.

The optimal flow configuration for a given diffusion filter constructedin accordance with the principles disclosed herein can be determined by,among other factors, the viscosity of each fluid, the relative requiredflow rates and velocities for each fluid, and the acceptable backpressure for each fluid source. For example, diffusion filters of thepresent invention may be used for dialysis wherein certain solutes areremoved from the blood. As referenced above, the first fluid can bedialysate and the second fluid can be blood. In some embodiments, suchas those exemplified by filter 2800 (FIG. 78), filter 4000 (FIG. 84) andfilter 6600 (FIG. 109), the dialysate can be pumped through the filter.In other embodiments, such as that exemplified by filter 5500 (FIG. 97),the filter may be submerged in a dialysate filled vessel. Theconfiguration of the first (dialysate) flow path can be constructed toachieve optimal flow rates for each of the above filter requirementsusing techniques previously herein described.

Similarly, in some applications, it can be desirable for the heart of apatient to act as the pump for the blood flow. This would necessitatethat the back pressure of the filter be appropriately low. If the heartof a patient is unable to provide the pressure required to achieveoptimal blood flow through a filter, an external pump may be used. If anexternal pump is used the filter can be configured to advantageously usethe increased pressure to achieve optimal performance. The design andconstruction of an optimized filter for these varying requirements maybe accomplished using methods and principles previously hereindescribed.

Additionally, certain patients with unique medical conditions canrequire removal from their blood of certain solutes which are notpresent in the absence of the medical conditions. Using the principlesand methods described previously herein, a diffusion filter can beconstructed in which laminas configured to remove these solutes areincluded in the filter. Indeed, the methods and principles disclosedherein enable the construction of highly efficient dialysis filterstailored to meet the unique requirements of any individual patient.

Thus, although there have been described particular embodiments of thepresent invention of new and useful tunable nanofiber filters, it is notintended that such referenced be construed as limitations upon the scopeof the invention.

1. A filter device, comprising: a housing defining an interior space,the housing having defined therein an inlet and an outlet, the inlet andoutlet each in fluid communication with the interior space; a pluralityof filter laminas disposed within the interior space, each filter laminaincluding an upper surface, a lower surface, a first peripheral portion,a second peripheral portion opposite the first peripheral portion, acentral region between the first and second peripheral portions, and anaperture defined through the first peripheral portion, the plurality offilter laminas arranged in a stack wherein: the aperture of theuppermost lamina is in fluid communication with the inlet, the apertureof the lowermost lamina is in fluid communication with the outlet, andthe opposing surfaces of adjacent filter laminas define a portion of aninterlaminar flow space extending between said opposing surfaces, theflow space in fluid communication with the apertures of thecorresponding adjacent filter laminas to form a continuous flow passageextending through the lamina stack from the inlet to the outlet; and anarray of nanofibers extending from a portion of each filter lamina intothe flow passage such that a fluid flowed through the flow passage flowsacross a portion of said array.
 2. The filter device of claim 1, whereinthe array of nanofibers extends into the flow passage from a portion ofthe upper surface of each filter lamina underlying the uppermost lamina,and a portion of the lower surface of each filter lamina overlying thelowermost lamina.
 3. The filter device of claim 1, wherein the filterlaminas are arranged in the stack such that the first peripheral portionof each filter lamina is proximal to the second peripheral portion ofeach corresponding adjacent filter lamina and the flow passage extendsthrough the stack in alternating directions between adjacent filterlaminas from the inlet to the outlet.
 4. The filter device of claim 3,wherein the first and second peripheral portions are a first end and asecond end opposite the first end, or a first longitudinal side and asecond longitudinal side opposite the first longitudinal side.
 5. Thefilter device of claim 4, wherein the plurality of filter laminascomprises a plurality of primary filter laminas and a secondary filterlamina, and wherein the uppermost filter lamina in the stack is thesecondary lamina.
 6. The filter device of claim 5, further comprising: aflow channel formed in the upper surface of each primary lamina, theflow channel including a downstream end and an upstream end opposite thedownstream end, said aperture extending through a portion of thedownstream end, the flow channel defining a portion of the interlaminarflow space; wherein the primary filter laminas are arranged in the stacksuch that the upstream end of each flow channel is in fluidcommunication with the aperture of a corresponding adjacent overlyingfilter lamina.
 7. The filter device of claim 4, further comprising aplurality of spacer laminas having an aperture defined through a centralportion thereof, each spacer lamina of the plurality disposed between acorresponding pair of adjacent filter laminas such that the centralaperture of each spacer lamina defines a portion of the interlaminarflow space between said corresponding pair of adjacent filter laminas.8. The filter device of claim 7, wherein the central region of the uppersurface of each filter lamina underlying the uppermost lamina comprisesa plurality of protrusions, the protrusions extending upwardly into aportion of the interlaminar flow space defined by the central apertureof a corresponding overlying adjacent spacer lamina.
 9. The filterdevice of claim 7, further comprising a plurality of longitudinal slotsdefined though a portion of the central region of each filter lamina,the slots in fluid communication with the interlaminar flow space toform a flow path extending axially through the lamina stack from thelongitudinal slots of the uppermost filter lamina to the longitudinalslots of the lowermost filter lamina.
 10. The filter device of claim 9,wherein: the array of nanofibers is a plurality of symmetrically opposedarrays of nanofibers formed on a portion of the upper and lower surfacesof each filter lamina adjacent to the longitudinal slots; and a firstfluid flowed through the flow passage is filtered of a solute bydiffusion of the solute across a portion of the array of nanofibers to asecond fluid flowed through the flow path.
 11. A diffusion filter fordialysis, comprising: a housing defining an interior space, the housinghaving defined therein first and second inlets and first and secondoutlets, the inlets and outlets in fluid communication with the interiorspace; an assembly of laminas disposed within the interior space, thelamina assembly comprising: a plurality of filter laminas, each filterlamina including a first and second slot defined therethrough, and aplurality of spacer laminas, each spacer lamina having a centralaperture defined therethrough; the filter and spacer laminas arrangedalternatingly in a stack wherein the central aperture of each spacerlamina defines an interlaminar space between opposing surfaces ofcorresponding adjacent filter laminas, the interlaminar space in fluidcommunication with the first and second slots of said adjacent filterlaminas such that the first slots form a first flow path extendingthrough the stack from the first inlet to the first outlet, and thesecond slots form a second flow path extending through the stack fromthe second inlet to the second outlet; a plurality of diffusion zonesformed in the interlaminar space, each diffusion zone comprising anarray of nanofibers extending into the interlaminar space from a portionof a corresponding adjacent filter lamina such that the array ofnanofibers separates the first and second flow paths throughout theinterlaminar flow space; wherein a first fluid flowed through the firstflow path interfaces across said diffusion zones with a second fluidflowed through the second flow path.
 12. The diffusion filter of claim11, wherein the first slot is a pair of parallel first slots definedthrough a central portion of each filter lamina, and the second slot ispositioned between the first slots.
 13. The diffusion filter of claim12, wherein each first slot has a first slot width, and the second slothas a second slot width greater than the first slot width such that thesecond fluid flows through the second flow path at a greater rate thanthe first fluid flows through the first flow path.
 14. The diffusionfilter of claim 11, wherein the first slot is defined through aperipheral portion of each filter lamina, and the second slot is aplurality of parallel second slots defined through a central portion ofeach filter lamina circumscribed by the peripheral portion, the firstslot perpendicular to the plurality of second slots.
 15. The diffusionfilter of claim 11, wherein when said first fluid interfaces with saidsecond fluid across said diffusion zone, a solute is filtered from thefirst fluid to the second fluid by diffusion of the solute across saiddiffusion zone.
 16. The diffusion filter of claim 12, furthercomprising: a plurality of first apertures defined through a portion ofeach filter lamina proximal to a lateral end of the first slots, thefirst apertures forming a secondary flow path for the first fluid; and aplurality of second apertures defined through a portion of each filterlamina proximal to a lateral end of the second slots, the secondapertures forming a secondary flow path for the second fluid; whereinthe first and second apertures create gradients within the diffusionzones.
 17. The diffusion filter of claim 12, wherein the first andsecond flow paths are substantially parallel and extend substantiallyaxially through the stack at an angle normal to a reference planecontaining the laminas.
 18. The diffusion filter of claim 14, whereinthe first flow path extends through the stack in alternating directionsthrough the interlaminar space between adjacent filter laminas from thefirst inlet to the first outlet, and the second flow path extendsaxially through the stack from the second inlet to the second outlet atan angle substantially normal to a reference plane containing thelaminas.
 19. The diffusion filter of claim 11, wherein: the first slotis a plurality of first slots defined through a first end of each filterlamina, and the second slot is a plurality of second slots definedthrough a second end of each filter lamina opposite the first end; thefilter laminas are arranged in the stack such that the first end of eachfilter lamina is proximal to the second end of each correspondingadjacent filter lamina and the first and second flow paths extendsthrough the stack in alternating directions between adjacent filterlaminas from the corresponding inlet to the corresponding outlet; andthe diffusion zones are configured to form a plurality of flow channelsextending through the interlaminar space between the first and secondends of corresponding adjacent filter laminas.
 20. The diffusion filterof claim 19, wherein the first and second flow paths counterflow throughthe interlaminar space of the stack in alternating directions betweenadjacent filter laminas from the corresponding inlet to thecorresponding outlet.
 21. The diffusion filter of claim 11, wherein: thefirst slot is defined through a first end of each filter lamina oppositea second end, and the second slot if a pair of lateral slots definedthrough opposing sides of each filter lamina between the first andsecond ends, the pair of second slots perpendicular to the first slot;at least one filter lamina of the plurality is a secondary filter laminahaving an array of nanoholes defined through a central portion thereofbetween the first and second ends and opposing sides, the array ofnanoholes in fluid communication with the aperture of a spacer lamina;and the first flow path extends through the stack in alternatingdirections through the interlaminar space between adjacent filterlaminas from the first inlet to the first outlet, and the second flowpath extends axially through the stack from the second inlet to thesecond outlet at an angle substantially normal to a reference planecontaining the laminas.
 22. A filter media comprising an assembly offilter laminas, each filter lamina including an upper surface, a lowersurface, an array of nanofibers form on a portion thereof, and anaperture extending from the upper surface to the lower surface, thefilter laminas arranged in a stacked orientation wherein the aperturesdefine a portion of a flow passage extending through the assembly andthe nanofibers extend into a portion of the flow passage to form ananoscale topography therein such that when a fluid containing aretentate is flowed through the flow passage, the retentate is filteredfrom the fluid.